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Medication Overdoses Leading to Emergency Department Visits Among Children

      Background

      The high prevalence of medication use increases the potential for medication overdoses, especially among children.

      Purpose

      This paper describes the burden of unintentional pediatric medication overdoses in order to target new prevention efforts.

      Methods

      Data were analyzed in 2007 and 2008 from the National Electronic Injury Surveillance System, collected January 1, 2004, through December 31, 2005, to estimate the number of emergency department visits resulting from unintentional medication overdoses among children aged ≤18 years in the U.S. These data were analyzed by patient demographics, overdose cause, and implicated products, and compared to visits for nonpharmaceutical consumer product poisonings.

      Results

      Based on 3034 cases, an estimated 71,224 emergency department visits for medication overdoses were made annually by children aged ≤18 years, representing 68.9% of emergency department visits for unintentional pediatric poisonings. The rate of unintentional poisonings from medications was twice the rate of those from nonpharmaceutical consumer products (9.2 visits per 10,000 individuals per year [95% CI=7.3, 11.0] vs 4.2 per 10,000 individuals per year [95% CI=3.3, 5.0]). Four fifths (82.2%) of visits for medication overdoses were from unsupervised ingestions (children accessing medications on their own); medication errors and misuse resulted in 14.3% of visits. Most visits (81.3%) involved children aged ≤5 years, and commonly available over-the-counter medications were implicated in one third (33.9%) of visits.

      Conclusions

      Medication overdoses among children, notably unsupervised ingestions, represent a substantial burden in terms of emergency department visits and hospitalizations. New efforts to prevent pediatric medication overdoses are needed.

      Introduction

      Outpatient medication use is increasingly common in the U.S., with 82% of adults and 56% of children taking at least one medication every week. Use of multiple medications has also increased, with the prevalence of use of five or more medications among adults rising from 22% to 31% between 2000 and 2004.

      Patterns of medication use in the United States, 2004: a report from the Slone Survey, Slone Epidemiology Center.

      The high frequency of medication usage and the rising number of medications stored in American homes increases the potential for medication overdoses in ambulatory settings, especially among children.
      Poison control center triage is currently performed to treat overexposure to many types of products—nonpharmaceutical consumer products such as cleaning substances, pesticides, and personal care products, as well as medication overdoses. Although there has been an overall decline in the number of calls to poison control centers for poisoning exposures among children aged ≤5 years, the proportion of calls for overexposures to medications has increased from 34% to 44% from 2002 to 2006.
      • Watson W.A.
      • Litovitz T.L.
      • Rodgers Jr, G.C.
      • Klein-Schwartz W.
      • Youniss J.
      • Rose S.R.
      • et al.
      2002 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System.
      • Bronstein A.C.
      • Spyker D.A.
      • Cantilena Jr, L.R.
      • Green J.
      • Rumack B.H.
      • Heard S.E.
      2006 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS).
      It has been previously estimated
      • Cohen A.L.
      • Budnitz D.S.
      • Weidenbach K.N.
      • et al.
      National surveillance of emergency department visits for outpatient adverse drug events in children and adolescents.
      that more than 70,000 children aged ≤18 years are treated in U.S. emergency departments for unintentional medication overdoses annually, but the underlying causes and risk factors for unintentional medication overdoses have not been well described. Studies have focused on unintentional poisoning exposures in children
      • Chien C.
      • Marriott J.L.
      • Ashby K.
      • Ozanne-Smith J.
      Unintentional ingestion of over the counter medications in children less than 5 years old.
      or on pediatric medication errors,
      • Heubi J.E.
      • Barbacci M.B.
      • Zimmerman H.J.
      Therapeutic misadventures with acetaminophen: hepatoxicity after multiple doses in children.
      • McPhillips H.A.
      • Stille C.J.
      • Smith D.
      • et al.
      Potential medication dosing errors in outpatient pediatrics.
      but nationally representative data on the scope, burden, and causes of medication overdoses are needed to help prioritize and target new efforts to prevent unintentional medication overdoses.
      CDC
      Assessing the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project—six sites, United States, January 1–June 15, 2004.
      In this report, a nationally representative public health surveillance system is used to describe outpatient pediatric medication overdoses that led to emergency department visits, and identify underlying causes. The magnitude of the burden of medication overdoses is described by comparing medication overdoses to unintentional poisonings from nonpharmaceutical consumer products.

      Methods

      Data Sources

      Cases of medication overdoses and nonpharmaceutical consumer product poisonings were identified using the U.S. Consumer Product Safety Commission's National Electronic Injury Surveillance System (NEISS). NEISS was created in 1971 for the purpose of estimating the national number of emergency department visits for product-related injuries by identifying cases from a national probability sample of hospitals that have a minimum of six beds and a 24-hour emergency department, in the U.S. and its territories.
      U.S. Consumer Product Safety Commission
      National Electronic Injury Surveillance System All Injury Program sample design and implementation.
      Trained coders at each hospital review clinical records of every emergency department visit. When physician-diagnosed adverse drug events (ADEs) are identified, coders report up to two drugs implicated, along with the ADE. They also record a narrative description of the incident. An ADE is defined as a condition that the treating physician attributed to the use of a drug or to a drug-specific effect.
      • Cohen A.L.
      • Budnitz D.S.
      • Weidenbach K.N.
      • et al.
      National surveillance of emergency department visits for outpatient adverse drug events in children and adolescents.
      These data constitute the Cooperative Adverse Drug Event Surveillance component (NEISS-CADES) of the surveillance system. When consumer product–related poisonings are identified, coders report the intent of product use, cause of injury, consumer products associated with the injury, and a narrative description of the incident. Cases were identified from the All Injury Program component (NEISS-AIP) of the surveillance system. A total of 63 hospitals participate in the NEISS-CADES/AIP sample; five (7.9%) of these are pediatric hospitals.
      Development, operation, and evaluation of both surveillance systems have been previously described.
      CDC
      Assessing the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project—six sites, United States, January 1–June 15, 2004.
      U.S. Consumer Product Safety Commission
      National Electronic Injury Surveillance System All Injury Program sample design and implementation.
      • Budnitz D.S.
      • Pollock D.A.
      • Weidenbach K.N.
      • Mendelsohn A.B.
      • Schroeder T.J.
      • Annest J.L.
      National surveillance of emergency department visits for outpatient adverse drug events.
      • Jhung M.A.
      • Budnitz D.S.
      • Mendelsohn A.B.
      • Weidenbach K.N.
      • Nelson T.D.
      • Pollock D.A.
      Evaluation and overview of the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance Project (NEISS-CADES).
      • Budnitz D.S.
      • Pollock D.A.
      • Mendelsohn A.B.
      • Weidenbach K.N.
      • McDonald A.K.
      • Annest J.L.
      Emergency department visits for outpatient adverse drug events: demonstration for a national surveillance system.
      • Schroeder T.J.
      • Ault K.
      National Electronic Injury Surveillance System (NEISS) sample design and implementation from 1997 to present.
      Data collection is managed by the U.S. Consumer Product Safety Commission in collaboration with the CDC (NEISS-CADES and NEISS-AIP) and the Food and Drug Administration (NEISS-CADES). Hospital participation in NEISS-CADES/AIP is voluntary and confidential (Consumer Product Safety Act, 15 U.S.C. 2051–2084). Data collection with NEISS was considered a public health surveillance activity and did not require IRB approval.

      Case Definitions

      A case was defined as presentation to an emergency department between January 1, 2004, and December 31, 2005, by a person aged ≤18 years for a condition that the treating physician attributed to a medication overdose (NEISS-CADES) or to poisoning from a nonpharmaceutical consumer product (NEISS-AIP). Medication overdoses were defined as exposure to more than the intended dose of a medication or inadvertent exposure to a medication. Cases included ingestions and dermal or ocular exposures. Emergency department visits resulting from intentional self-harm, recreational drug use, and drug addiction were excluded.
      Medications included prescription and nonprescription pharmaceuticals, vitamins, herbals, and dietary supplements; they excluded illicit substances, alcohol, and tobacco. Nonpharmaceutical consumer products included potentially toxic substances such as cleaning substances, pesticides, and personal care products; they excluded illicit substances, alcohol, tobacco, botanicals, bee stings, and lead.

      Measures

      Patient age, gender, and race; the implicated product; clinical management; and disposition were identified by emergency department record abstraction by NEISS coders.
      CDC
      Assessing the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project—six sites, United States, January 1–June 15, 2004.
      • Jhung M.A.
      • Budnitz D.S.
      • Mendelsohn A.B.
      • Weidenbach K.N.
      • Nelson T.D.
      • Pollock D.A.
      Evaluation and overview of the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance Project (NEISS-CADES).
      • Budnitz D.S.
      • Pollock D.A.
      • Mendelsohn A.B.
      • Weidenbach K.N.
      • McDonald A.K.
      • Annest J.L.
      Emergency department visits for outpatient adverse drug events: demonstration for a national surveillance system.
      Children were considered hospitalized if they were admitted to a hospital ward, assigned emergency department observation admission status, or transferred to another facility for medical care. The underlying causes of overdoses were identified by review of the abstracted clinical summary, chief complaint, and verbatim diagnoses; they were categorized as unsupervised ingestions, medication errors, or misuse. An unsupervised ingestion was defined as ingestion of a medication by a child aged <12 years without adult supervision. A medication error was defined as an unintended mistake in medication management, including using an incorrect dose, incorrect medication/formulation, incorrect dosing schedule, and error in prescribing or dispensing (provider/pharmacy error). Misuse was defined as intentional use of a medication in a manner inconsistent with how it should have been used, such as using a medication prescribed for another individual or using higher doses than recommended. Misuse and errors were not attributed to children aged <12 years. Overdoses not falling into any of these categories or otherwise not described were categorized as other/unspecified.

      Statistical Analysis

      Because NEISS is a probability sample of U.S. hospitals, an estimated total number of emergency department visits nationally (referred to as national estimates or estimated visits) may be calculated by assigning each NEISS-CADES and NEISS-AIP case a sample weight based on the inverse probability of hospital selection. These weights are adjusted annually for hospital response rates and hospital closures and mergers.
      U.S. Consumer Product Safety Commission
      National Electronic Injury Surveillance System All Injury Program sample design and implementation.
      During 2007 and 2008, national estimates of emergency department visits during the period from 2004 to 2005 and the corresponding 95% CIs were calculated using Surveymeans and a direct variance estimation procedure in SAS version 9.1 to account for weighting and the complex sample design. Because data were collected over the 2-year period, these estimates were summed, and the sum was divided by 2 to determine annual national estimates. Population rates were calculated using projected 2004 and 2005 population estimates from the U.S. Census Bureau.

      U.S. Census Bureau. U.S. interim projections by age, sex, race, and Hispanic origin, detail file.

      National estimates based on <20 cases or with a coefficient of variation >30% were considered statistically unstable and are not reported.
      • Schroeder T.J.
      • Ault K.
      National Electronic Injury Surveillance System (NEISS) sample design and implementation from 1997 to present.

      Results

      Based on 3034 sample cases, an estimated 71,224 emergency department visits were made annually by children aged ≤18 years for unintentional medication overdoses. Based on 1405 sample cases, an estimated 32,217 emergency department visits were made annually for unintentional poisonings from nonpharmaceutical consumer products (Table 1). Medication overdoses accounted for 68.9% of emergency department visits for unintentional poisonings in this age group. Most emergency department visits for medication overdoses (81.3%) and nonpharmaceutical consumer product poisonings (92.3%) occurred among children aged ≤5 years.
      Table 1Emergency department visits by children for medication overdoses and nonpharmaceutical product overexposures, U.S., 2004–2005
      Patient characteristicsEmergency department visits for medication overdoses
      Case counts and estimates for medications from the 2004–2005 National Electronic Injury Surveillance System–Cooperative Adverse Drug Event Surveillance project, CDC. Medications refer to prescription or nonprescription pharmaceuticals, vitamins, herbals, and dietary supplements.
      Emergency department visits for unintentional nonpharmaceutical product overexposures
      Case counts and estimates from the 2004–2005 National Electronic Injury Surveillance System–All Injury Program, CDC. Nonpharmaceutical products refer to cleaning substances, pesticides, personal care products, and other potentially toxic substances, excluding illicit substances, alcohol, tobacco, botanicals, bee stings, and lead.
      CasesAnnual national estimatePopulation rate per 10,000 individuals
      Population estimates based on the average of 2004 and 2005 mid-year U.S. Census estimates from the National Center for Health Statistics, CDC.
      CasesAnnual national estimatePopulation rate per 10,000 individuals
      Population estimates based on the average of 2004 and 2005 mid-year U.S. Census estimates from the National Center for Health Statistics, CDC.
      nn (%)n (95% CI)nn (%)n (95% CI)
      Age (years)
       <11774,313 (6.1)10.5 (7.9, 13.1)1092,779 (8.6)6.8 (4.0, 9.5)
       174317,557 (24.7)43.2 (32.9, 53.5)63814,733 (45.7)36.2 (27.5, 44.9)
       292421,980 (30.9)54.7 (42.7, 66.6)3297,571 (23.5)18.8 (13.9, 23.8)
       34089,721 (13.6)24.1 (18.9, 29.4)1192,786 (8.6)6.9 (4.9, 8.9)
       41522,845 (4.0)7.1 (5.1, 9.2)63920 (2.9)2.3 (1.2, 3.4)
       5791,512 (2.1)3.9 (2.7, 5.1)37939 (2.9)2.4 (1.4, 3.4)
       6–112375,418 (7.6)2.3 (1.6, 2.9)43699 (2.2)0.3 (0.2, 0.4)
       12–141062,282 (3.2)1.8 (1.1, 2.4)23606 (1.9)0.5 (0.2, 0.7)
       15–182085,596 (7.9)3.3 (2.5, 4.2)441,183 (3.7)0.7 (0.5, 0.9)
      Gender
      Unknown for one case
       Female1,43032,978 (46.3)8.7 (7.0, 10.4)56113,202 (41.0)3.5 (2.7, 4.3)
       Male1,60338,206 (53.6)9.6 (7.5, 11.8)84419,015 (59.0)4.8 (3.9, 5.7)
      Race
       White1,37736,718 (51.5)6.1 (4.2, 8.0)43612,434 (38.6)2.1 (1.3, 2.8)
       Black/African-American6268,653 (12.1)6.8 (4.1, 9.6)4817,122 (22.1)5.6 (2.9, 8.4)
       Unspecified96623,694 (33.3)2758,844 (27.5)
       Other652,159
      Rates are not calculated for estimates with coefficient of variation > 30% or based on <20 cases(—), and estimates for which a denominator was not available.
       (3.0)
      Rates are not calculated for estimates with coefficient of variation > 30% or based on <20 cases(—), and estimates for which a denominator was not available.
      2133,817
      Rates are not calculated for estimates with coefficient of variation > 30% or based on <20 cases(—), and estimates for which a denominator was not available.
       (11.8)
      Rates are not calculated for estimates with coefficient of variation > 30% or based on <20 cases(—), and estimates for which a denominator was not available.
      Disposition
      Unknown for one case
       Admitted, observed, or transferred54511,081 (15.6)1.4 (1.0, 1.9)1192,514 (7.8)0.3 (0.2, 0.4)
       Treated and released, or left against medical advice2,48960,144 (84.4)7.8 (6.1, 9.4)1,28529,697 (92.2)3.8 (3.1, 4.6)
      Total3,03471,224 (100)9.2 (7.3, 11.0)1,40532,217 (100.0)4.2 (3.3, 5.0)
      a Case counts and estimates for medications from the 2004–2005 National Electronic Injury Surveillance System–Cooperative Adverse Drug Event Surveillance project, CDC. Medications refer to prescription or nonprescription pharmaceuticals, vitamins, herbals, and dietary supplements.
      b Case counts and estimates from the 2004–2005 National Electronic Injury Surveillance System–All Injury Program, CDC. Nonpharmaceutical products refer to cleaning substances, pesticides, personal care products, and other potentially toxic substances, excluding illicit substances, alcohol, tobacco, botanicals, bee stings, and lead.
      c Population estimates based on the average of 2004 and 2005 mid-year U.S. Census estimates from the National Center for Health Statistics, CDC.
      d Unknown for one case
      e Rates are not calculated for estimates with coefficient of variation > 30% or based on <20 cases (—), and estimates for which a denominator was not available.
      The population rate of emergency department visits for medication overdoses was twice that for nonpharmaceutical consumer products (9.2 visits per 10,000 individuals per year [95% CI=7.3, 11.0] vs 4.2 per 10,000 individuals per year [95% CI=3.3, 5.0]). Population rates of emergency department visits for medication overdoses were highest among children aged 2 years (54.7 per 10,000 individuals per year); the rate declined with increasing age, reaching a nadir for children aged 12–14 years (1.8 per 10,000 individuals per year; Figure 1). Medication overdose rates increased during adolescence, with children aged 15–18 years having nearly twice the rate of children aged 12–14 years (3.3 per 10,000 individuals per year [95% CI=2.5, 4.2] vs 1.8 per 10,000 individuals per year [95% CI=1.1, 2.4]).
      Figure thumbnail gr1
      Figure 1Differences in rates of emergency department visits for medication overdoses and nonpharmaceutical product overexposures in children, by age category; population rate estimates based on the average of 2004 and 2005 mid-year U.S. Census estimates from the National Center for Health Statistics, CDC; bars represent 95% CIs
      African-American children had similar rates of emergency department visits for medication overdoses and nonpharmaceutical consumer product poisonings (6.8 per 10,000 individuals per year [95% CI=4.1, 9.6] vs 5.6 per 10,000 individuals per year [95% CI=2.9, 8.4]). For Caucasian children, the rate of emergency department visits for medication overdoses was three times higher than that for nonpharmaceutical consumer product poisonings (6.1 per 10,000 individuals per year [95% CI=4.2, 8.0] vs 2.1 per 10,000 individuals per year [95% CI=1.3, 2.8]).
      The rate of hospitalizations for medication overdoses was four times higher than that for poisonings from nonpharmaceutical consumer products (1.4 per 10,000 individuals per year [95% CI=1.0, 1.9] vs 0.3 per 10,000 individuals per year [95% CI=0.2, 0.4]). Most hospitalizations (9249 estimated visits annually; 83.5% [95% CI=79.4%, 87.5%]) were among children aged ≤5 years. Nearly one third (29.2%) of children treated for unintentional medication overdoses received gastrointestinal decontamination, almost exclusively with activated charcoal.
      Unsupervised medication ingestions caused 82.2% (95% CI=80.1%, 84.3%) of emergency department visits from medication overdoses (58,550 estimated visits annually, 7.6 visits per 10,000 individuals per year [95% CI=6.0, 9.1]; Table 2). Medication errors caused 8.0% (95% CI=6.8%, 9.2%) of emergency department visits (5691 estimated visits annually, 0.7 visits per 10,000 individuals per year [95% CI=0.6, 0.9]); medication misuse caused 6.3% (95% CI=5.0%, 7.6%) of emergency department visits (4469 estimated visits annually, 0.6 visits per 10,000 individuals per year [95% CI=0.4, 0.7]). The causes of the remaining medication overdoses were unspecified (3.5% [95% CI=1.9%, 5.1%], 2515 estimated visits annually). Hospitalization rates for unsupervised ingestions, misuse, and medication errors were similar (15.8%, 14.9%, and 10.0%, respectively [95% CI=11.4, 20.2; 4.0, 25.9; and 5.4, 14.6, respectively]).
      Table 2Emergency department visits by children for medication overdoses, U.S., 2004–2005
      Case counts and estimates for medications from the 2004–2005 National Electronic Injury Surveillance System–Cooperative Adverse Drug Event Surveillance project, CDC. Estimates with coefficient of variation >30% or based on <20 cases are not calculated (—).
      Patient age (years)Unsupervised ingestionMedication errorsMisuseUnspecified
      CasesAnnual national estimate (58,550 visits)CasesAnnual national estimate (5691 visits)CasesAnnual national estimate (4469 visits)CasesAnnual national estimate (2515 visits)
      n (%)95% CIn (%)95% CIn (%)95% CIn (%)95% CI
      <1119 (69.7)(60.9, 78.4)54 (26.4)(18.1, 34.7)04 (—)
      1–52225 (97.0)(96.1, 97.9)60 (2.2)(1.5, 3.0)1
      Caregiver responsible for misuse
      20 (0.8)(0.3, 1.2)
      6–11139 (65.2)(52.7, 77.7)64 (20.7)(13.2, 28.2)1
      Caregiver responsible for misuse
      33 (14.0)
      12–180 (—)82 (28.4)(21.0, 35.8)17856.6(47.6, 65.6)54 (15.0)(7.0, 23.0)
      a Case counts and estimates for medications from the 2004–2005 National Electronic Injury Surveillance System–Cooperative Adverse Drug Event Surveillance project, CDC. Estimates with coefficient of variation >30% or based on <20 cases are not calculated (—).
      b Caregiver responsible for misuse
      Unsupervised ingestions caused nearly all (97%) of the emergency department visits among children aged 1–5 years (Table 2). Although unsupervised ingestions accounted for a smaller proportion of overdoses among children aged <1 year or 6–11 years, they remained the most common cause of overdose, causing 69.7% and 65.2% of overdoses, respectively, in these groups. Medication errors caused approximately one fourth of medication overdoses among infants aged <1 year, but only 2.2% of overdoses among children aged 1–5 years (Table 2). Errors accounted for 28.4% of overdoses among children aged 12–18 years. Misuse caused 56.6% of medication overdoses among children aged 12–18 years.
      The most common type of medication error was administration of the incorrect dose (113 cases, 43.7% of visits from errors). Of the cases involving dosing errors, 14 cases (12.4%) resulted from misplacing decimal points, as in administration of 5 mL instead of 0.5 mL; and 7 cases (6.2%) resulted from using incorrect units of volume, as in using a tablespoon rather than a teaspoon. The second most common type of error was administration of the incorrect medication or formulation (79 cases, 33.2% of visits from errors), followed by use of an incorrect schedule of administration (32 cases, 11.4% of visits from errors).
      The four medications most frequently implicated in overdoses were acetaminophen (7226 estimated visits annually, 9.3% [95% CI=7.9%, 10.8%]); cough and cold medications (5650 estimated visits annually; 7.3% [95% CI=5.7%, 8.9%]); antidepressants (4737 estimated visits annually, 6.1% [95% CI=4.8%, 7.5%]); and nonsteroidal anti-inflammatory drugs (NSAIDs) (4083 estimated visits annually, 5.3% [95% CI=4.1%, 6.4%]). Unsupervised ingestions were the underlying cause of the overdose in over 80% of these emergency department visits (Figure 2). Oral medications commonly available over-the-counter (which included acetaminophen, non-opioid and noncarbinoxamine cough and cold medications, NSAIDs, antihistamines, vitamins/minerals, aspirin, and other non-opioid analgesics) were implicated in an estimated 26,162 visits annually, accounting for 33.9% of all visits (95% CI=31.1%, 36.6%); and in 35.9% of visits for unsupervised ingestions (95% CI=32.8%, 39.0%; Table 3). Nearly half (2606 estimated visits annually, 42.2% [95% CI=32.0%, 52.3%]) of visits for medication errors involved central nervous system agents (which included anticonvulsants, antidepressants, antipsychotics, stimulants, opioids/benzodiazepines, alpha adrenergic agents, and miscellaneous central nervous system agents), whereas analgesics (acetaminophen, NSAIDs, opioids, aspirin, and non-opioid analgesics) were the most commonly implicated type of medication among misuse cases (2138 estimated visits annually, 43.0% [95% CI=33.3%, 52.6%]).
      Figure thumbnail gr2
      Figure 2Overdose cause for the four medication classes most commonly implicated in pediatric medication overdoses; cough and cold agents include over-the-counter and prescription combination drugs
      NSAIDs, nonsteroidal anti-inflammatory drugs
      Table 3Medications most commonly implicated in emergency department visits for overdoses in children, U.S., 2004–2005
      Case counts from the 2004–2005 National Electronic Injury Surveillance System–Cooperative Adverse Drug Event Surveillance project, CDC. For 336 cases(annual estimate, 6028 visits), two drugs were implicated in the adverse event. Percentages calculated with a denominator of all implicated drugs(3370 drugs).
      Unsupervised ingestionMedication errorMisuse
      Drug classCasesDrug classCasesDrug classCases
      n (%)n (%)n (%)
      Acetaminophen289 (10.5)Anticonvulsants29 (10.0)NSAIDs33 (15.8)
      Opioids/benzodiazepines211 (7.7)Cough and cold agents
      Includes over-the-counter and prescription combination drugs
      29 (10.0)Acetaminophen28 (13.5)
      Cough and cold agents
      Includes over-the-counter and prescription combination drugs
      202 (7.4)Antipsychotics19 (6.6)Opioids/benzodiazepines18 (8.7)
      NSAIDs167 (6.1)Opioids/benzodiazepines18 (6.2)Cough and cold agents
      Includes over-the-counter and prescription combination drugs
      13 (6.3)
      Antidepressants161 (5.9)Antidepressants16 (5.6)Miscellaneous central nervous system agents11 (5.3)
      Antihistamines160 (5.8)Stimulants16 (5.6)Antidepressants10 (4.8)
      Antihypertensives
      Includes beta-blockers, calcium channel blockers, hydralazine, and unnamed antihypertensives
      149 (5.4)Insulin14 (4.8)Antihistamines10 (4.8)
      Unknown agents133 (4.8)Alpha-2 adrenergic agonists
      Includes clonidine and guanfacine
      14 (4.8)Aspirin10 (4.8)
      Vitamins/nutrients125 (4.6)Antihypertensives
      Includes beta-blockers, calcium channel blockers, hydralazine, and unnamed antihypertensives
      13 (4.5)Miscellaneous non-opioid or unnamed analgesics10 (4.8)
      Topical agents98 (3.6)Metoclopramide12 (4.2)Anticonvulsants9 (4.3)
      NSAIDs, nonsteroidal anti-inflammatory drugs
      a Case counts from the 2004–2005 National Electronic Injury Surveillance System–Cooperative Adverse Drug Event Surveillance project, CDC. For 336 cases (annual estimate, 6028 visits), two drugs were implicated in the adverse event. Percentages calculated with a denominator of all implicated drugs (3370 drugs).
      b Includes over-the-counter and prescription combination drugs
      c Includes beta-blockers, calcium channel blockers, hydralazine, and unnamed antihypertensives
      d Includes clonidine and guanfacine

      Discussion

      Between 2004 and 2005, medications caused an estimated 68.9% of all emergency department visits for unintentional poisonings (9.2 visits per 10,000 individuals per year). Most emergency department visits for medication overdoses occurred among children aged ≤5 years (estimated 57,928 emergency department visits annually, 81.3%). Four fifths (82.2%) of emergency department visits for medication overdoses were from unsupervised ingestions, and nonprescription medications were implicated in 35.9%. The fact that, annually, one of every 180 children aged 2 years (54.7/10,000 individuals) is treated in an emergency department for a medication overdose, despite current prevention efforts, underscores the size of this public health issue. Further, these data reflect visits to only emergency departments. Poison control centers receive 1.5 million calls for pediatric overexposures of all types annually, and approximately three fourths of calls are managed over the telephone and do not result in direct treatment by a healthcare professional.
      • Bronstein A.C.
      • Spyker D.A.
      • Cantilena Jr, L.R.
      • Green J.
      • Rumack B.H.
      • Heard S.E.
      2006 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS).
      Because unsupervised ingestions by children aged ≤5 years account for over three fourths of pediatric outpatient medication overdoses, efforts should focus on preventing unsupervised ingestions in this age group. Strategies to prevent injuries such as pediatric medication overdoses may be categorized as engineering (modifying the product or how it is stored or accessed); education (convincing individuals to change their behavior); or enforcement (enacting regulations that modify individual behavior). Because young children's curiosity and hand-to-mouth behavior place them at increased risk for unsupervised ingestions,
      • Angalakuditi M.V.
      • Coley K.C.
      • Krenzelok E.P.
      Children's acetaminophen exposures reported to a regional poison control center.
      • Agran P.F.
      • Winn D.
      • Anderson C.
      • Trent R.
      • Walton-Haynes L.
      Rates of pediatric and adolescent injuries by year of age.
      • McFee R.B.
      • Caraccio T.R.
      “Hang Up Your Pocketbook”—an easy intervention for the granny syndrome: grandparents as a risk factor in unintentional pediatric exposures to pharmaceuticals.
      engineering strategies to prevent children's access to medications can be particularly attractive as these are commonly passive approaches that do not require human behavior change.
      • Baker S.P.
      Childhood injuries: the community approach to prevention.
      • Budnitz D.S.
      • Layde P.M.
      Outpatient drug safety: new steps in an old direction.
      Poison treatment in the home American Academy of Pediatrics Committee on Injury, Violence, and Poison Prevention.
      • Tenenbein M.
      Unit-dose packaging of iron supplements and reduction of iron poisoning in young children.
      Child-resistant packaging is an engineering strategy that has been made a regulatory requirement for many medications and other products implicated in children's poisonings
      • Mrvos R.
      • Krenzelok E.P.
      Child-resistant closures for mouthwash: do they make a difference?.
      • Liebelt E.L.
      • DeAngelis C.D.
      Evolving trends and treatment advances in pediatric poisoning.
      • Paulozzi L.J.
      Overdoses are injuries too.
      ; it is estimated to have reduced the child mortality rate from accidental overdose of prescription drugs by 45% between 1974 and 1992.
      • Rodgers G.B.
      The safety effects of child-resistant packaging for oral prescription drugs Two decades of experience.
      However, limitations of current child-resistant packaging have been described, and they include children's ability to gain access to items stored in such packaging even when it is properly closed.
      • Chien C.
      • Marriott J.L.
      • Ashby K.
      • Ozanne-Smith J.
      Unintentional ingestion of over the counter medications in children less than 5 years old.
      • Lembersky R.B.
      • Nichols M.H.
      • King W.D.
      Effectiveness of child-resistant packaging on toxin procurement in young poisoning victims.
      Educational efforts have tried to address limitations of current child-resistant packaging by reminding parents and caregivers to keep medications in their original containers and to always securely replace child-resistant caps.
      CDC
      Nonfatal, unintentional medication exposures among young children—United States, 2001–2003.
      These data demonstrate that despite current child-resistant packaging technology and parental education, unsupervised ingestions of products remain a public health problem.
      Passive engineering innovations that could be evaluated to determine their effectiveness in preventing pediatric medication overdoses have been described previously.
      • Schaefer M.K.
      • Shehab N.
      • Cohen A.L.
      • Budnitz D.S.
      Adverse events from cough and cold medications in children.
      One innovation is the use of adaptors on bottles of liquid medication so that the medication can be accessed only with a needleless syringe, thereby discouraging unsupervised young children from drinking directly from the bottle and reducing the amount they ingest if they do drink from the bottle. Use of unit-dose packaging may also reduce the amount an unsupervised child could ingest. The national data presented here suggest that the testing of these packaging innovations should initially focus on the medications most commonly implicated in pediatric overdoses, such as over-the-counter products.
      Although medication errors caused far fewer emergency department visits than unsupervised ingestions, these data point to error-reduction interventions that could be evaluated. Most medication errors were caused by incorrect dosing (43.7%) or inadvertent administration of an incorrect product (33.2%). Both types of errors are potentially preventable with engineering strategies. Unit-dose packaging could reduce dosing errors but may be impractical for products with wide dosing ranges.
      • Miller M.R.
      • Robinson K.A.
      • Lubomski L.H.
      • Rinke M.L.
      • Pronovost P.J.
      Medication errors in paediatric care: a systematic review of epidemiology and an evaluation of evidence supporting reduction strategy recommendations.
      Making Health Care Safer: A Critical Analysis of Patient Safety Practices Evidence Report/Technology Assessment, No. 43.
      Dispensing a dosing device that shows only units that correspond to those used in the accompanying prescription
      • McMahon S.R.
      • Rimsza M.E.
      • Bay R.C.
      Parents can dose liquid medication accurately.
      and that accommodates a volume nearly equivalent to a dose is another potential intervention that could be evaluated. Potential prevention strategies to address administration of an incorrect product include unambiguous product labeling and clearly differentiating product packaging for different members of a household.
      • Ozanne-Smith J.
      • Day L.
      • Parsons B.
      • Tibballs J.
      • Dobbin M.
      Childhood poisoning: access and prevention.
      Although rates of outpatient medication overdoses are highest among children aged ≤5 years, rates rise again as children proceed through adolescence. Parents and caregivers may perceive adolescents to have the maturity necessary for medication administration; however, these data suggest that at least some adolescents may lack the judgment to take medication without adult supervision. Because misuse caused most medication overdoses among children aged 12–18 years (56.6%), counseling on proper medication administration, incorporated into routine anticipatory guidance during health supervision visits, might help prevent medication overdoses among adolescents. Educational approaches to address medication misuse in adolescents could be provided through school health curricula, public service announcements, or current poison control center outreach activities.
      • Krenzelok E.P.
      The use of poison prevention and education strategies to enhance the awareness of the poison information center and to prevent accidental pediatric poisonings.
      Medication overdose surveillance with NEISS-CADES has several limitations that likely underestimate the burden of outpatient pediatric medication overdoses. NEISS-CADES captures medication overdoses resulting in emergency department visits but misses cases in which the patient does not receive medical attention (including those who die before receiving medical attention) or is evaluated only in an outpatient setting. However, the emergency department is likely the most appropriate single setting to ascertain severe, acute outpatient medication overdoses. Although NEISS-CADES has relatively low sensitivity for identifying certain ADEs (e.g., attributing gastrointestinal bleeding to warfarin or NSAIDS),
      • Jhung M.A.
      • Budnitz D.S.
      • Mendelsohn A.B.
      • Weidenbach K.N.
      • Nelson T.D.
      • Pollock D.A.
      Evaluation and overview of the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance Project (NEISS-CADES).
      cases of medication overdoses among children are probably more easily identified in the emergency department. Nonetheless, correctly identifying overdoses requires parents, children, and adolescents to be forthcoming about their exposure to medication; emergency department clinicians to correctly diagnose and document medication overdoses; and NEISS-CADES coders to correctly interpret and report the diagnoses and supporting clinical information. A final limitation is the potential for misclassification. It is possible that some cases of misuse among adolescents actually represent intentional overdoses but because the adolescent was not forthcoming about their intentions, these cases were inappropriately coded as unintentional.
      Medication overdoses among children, notably unsupervised ingestions, represent a substantial public health burden in terms of emergency department visits and hospitalizations. However, much of the morbidity from medication overdoses is potentially preventable through renewed injury-prevention efforts. New engineering approaches targeting unsupervised ingestions by children aged ≤5 years and the medications most commonly implicated may have the greatest impact in reducing the burden of outpatient pediatric medication overdoses.
      We thank Kelly Weidenbach, MPH, and Victor Johnson (Northrop-Grumman contractors for the CDC); J. Lee Annest, PhD, and Tadesse Haileyesus, MS, of CDC; Tom Schroeder, MS, Cathy Irish, BS, and Joel Friedman, BA, of the U.S. Consumer Product Safety Commission (CPSC); staff members of the Office of Statistics and Programming, National Center for Injury Prevention and Control, CDC; and staff members of the Division of Hazard and Injury Data Systems, U.S. Consumer Product Safety Commission for assistance with data collection and programming.
      This work was implemented using CDC funding and was supported in part by an appointment (Dr. Shehab) to the CDC Research Participation Program administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the CDC. None of the funding sources had a role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the funding agencies.
      Sarah Schillie discloses that she owns stock in Pfizer, Eli Lilly, Monsanto, General Electric, and Walgreen's, and that she previously owned stock in Abbott. Karen Thomas reports she owns stock in Baxter. The other authors report no financial disclosures.

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