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Division of Emergency Medicine, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati, Cincinnati, OHDrug and Poison Information Center, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
To understand which medications, under which circumstances, are responsible for the noted increase in pediatric medication poisonings, resource use, and morbidity.
Study design
Patient records from 2001-2008 were obtained from the National Poison Data System of the American Association of Poison Control Centers for children aged ≤5 years evaluated in a health care facility following exposure to a potentially toxic dose of a pharmaceutical agent. Pharmaceutical agents were classified as over-the-counter or prescription and by functional category. Exposures were classified as child self-ingested the medication or as therapeutic error. For the 8-year period, emergency visits, admissions, significant injuries, and trends in these events were calculated for each substance category.
Results
We evaluated 453 559 children for ingestion of a single pharmaceutical product. Child self-exposure was responsible for 95% of visits. Child self-exposure to prescription products dominated the health care impact with 248 023 of the visits (55%), 41 847 admissions (76%), and 18 191 significant injuries (71%). The greatest resource use and morbidity followed self-ingestion of prescription products, particularly opioids, sedative-hypnotics, and cardiovascular agents.
Conclusions
Prevention efforts have proved to be inadequate in the face of rising availability of prescription medications, particularly more dangerous medications.
Despite a half-century of dedicated preventive efforts, poisoning remains a common childhood injury. Each year, >500 000 children aged ≤5 years are exposed to pharmaceuticals in a potential poisoning event.
NPDS Annual Reports of the American Association of Poison Control Centers 1990-2008. Available from http://www.aapcc.org/dnn/NPDSPoisonData/NPDSAnnualReports.aspxAccessed on May 24, 2010. (For 2006-2008, the classic version of Table 22 of the report was obtained from the AAPCC.)
NPDS Annual Reports of the American Association of Poison Control Centers 1990-2008. Available from http://www.aapcc.org/dnn/NPDSPoisonData/NPDSAnnualReports.aspxAccessed on May 24, 2010. (For 2006-2008, the classic version of Table 22 of the report was obtained from the AAPCC.)
Calls to poison centers about pediatric pharmaceutical exposures (per 1 million population served) fell continuously from 1990-2000 but rose from 2001-2008.
National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, WISQARS Nonfatal Injury Reports. Available from http://webappa.cdc.gov/sasweb/ncipc/nfirates2001.html. Accessed October 18, 2010.
If we are to make progress in reducing childhood injury from pharmaceutical poisoning, we need to better understand the epidemic. To appropriately focus efforts, we need to know the medications that are the most consequential—those that contribute the most ED visits, hospitalization, and harm. Our objective was to understand which medications, under which circumstances, are responsible for the increase in pediatric medication poisonings, resource use, morbidity, and mortality so that investigators and policy makers can most effectively assess and revise preventive efforts.
Methods
The National Poison Data System (NPDS) is the electronic database of all calls to any member poison center of the American Association of Poison Control Centers (AAPCC). These centers provide service throughout the United States and cover every citizen. Data from every call are recorded electronically, in real time, in a standardized format. NPDS was searched for all electronic medical records meeting the following criteria: children aged ≤5 years whose call type was an unintentional exposure to a pharmaceutical agent that involved presenting to a health care facility in 2001-2008. Because the health care facilities involved in evaluating these patients are overwhelmingly EDs, that term is used throughout this report.
Detailed analysis of these records was limited to those exposed by ingestion, to agent type (over-the-counter [OTC] or prescription), to standardized reason code Unintentional Self-Exposure or Unintentional Therapeutic Error, and those exposed to a single product. Products sold in combination (eg, antihistamine/decongestant cough and cold products) were considered a single product and included in the analysis. Acetaminophen-containing combination cough and cold products were included as cough and cold products.
To further assess the impact of each class of agent and reason for ingestion, we calculated the percent that were admitted (proxy for higher resource use) and the morbidity—the percent meeting NPDS standardized symptom-based outcome criteria for moderate effect, major effect, or death (defined in the NPDS Annual Report, Appendix B).
These patients were considered injured. For all deaths, one of the authors (G.B.) obtained and reviewed additional information from the published AAPCC annual reports, death reports provided by the AAPCC, and information collected for a prior study, in order to validate the nature of exposure, the reason, and the primary agent.
Cases were excluded if the additional information suggested the drug exposure was not related to the patient’s death or exposure route was not ingestion.
To assess for the impact of outside trends on results, we compared changes in ED visits, injuries, and hospitalizations from 2001-2008 to changes in the pediatric population of the United States
National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, WISQARS Nonfatal Injury Reports. Available from http://webappa.cdc.gov/sasweb/ncipc/nfirates2001.html. Accessed October 18, 2010.
To compare the rate of change in one category of medication, opioids, we used publically available data on US opioid use (distribution from manufacturers and distributors reports of Schedule II and III narcotics to US Department of Justice, Drug Enforcement Administration’s Automation of Reports and Consolidated Orders System [ARCOS] requested at http://www.deadiversion.usdoj.gov/arcos/index.html).
From an SQL database of the records, summary data were compiled using Excel 2010 (Microsoft Corporation, Redmond, Washington) and imported to SAS (Statistical Analysis System v9.2; SAS Institute, Cary, North Carolina). General linear models using least squares regression analysis were used to analyze trends and trend comparisons. Comparisons of proportions were done using χ2 tests. All statistical analyses were conducted with SAS. Comparisons were not considered significant unless P < .05.
Approval for data use was obtained from the AAPCC Data Access Committee and the board of directors. Data were provided to the investigators in a coded fashion to maintain blinding to the individuals and poison centers. The study was also reviewed by the institutional review board at Cincinnati Children’s Hospital Medical Center and deemed exempt.
Results
In this 8-year study period, 544 133 children aged ≤5 years were exposed to pharmaceuticals and documented to have reached and received care at an ED. Of these, 453 559 ingested a single product so that the symptoms, management, and outcome could be definitively ascribed to that agent alone (Figure 1).
Figure 1ED visits by children aged ≤5 years following unintentional pharmaceutical exposure 2001-2008: patient distribution.
Table I (available at www.jpeds.com) details the ages, sex, origin of poison center involvement, admission rate, and injury rate for these groups. Victims of therapeutic errors were younger, disproportionately boys, and more likely to have been identified at the hospital than were children who self-ingested medication. Overall, 48% of poison center involvement originated from the ED and 45% originated from the patient’s own residence, before travel to the ED.
Child self-exposure to prescription products represented the largest health care impact, with 248 023 ED visits (55%), 41 847 admissions (76%), and 18 191 injuries (71%). Admission was to an intensive care unit in 43% of admissions following self-exposure to prescription medications and in 34%, 41%, and 35% of admissions following self-exposure to OTC medications, therapeutic errors with prescription medications, and therapeutic errors with OTC medications, respectively.
Considering the 67 080 patients who were excluded from the detailed analysis, 64 017 were excluded because the patient ingested >1 medication. Of these, 97% were from self-ingestion and 87% of these ingested at least 1 prescription product. Twenty-three percent were admitted and 8% sustained an injury. In 48% of cases, contact with the poison center was initiated after presentation to the ED. The other 3063 patients included 1006 ingestions of 1 street drug and 2057 prescription or OTC ingestions with other unintentional reasons listed.
Figure 2 shows the overall trend from baseline for exposures (including those managed at home), ED evaluations, admissions, injuries, and the US population of children aged ≤5 years. The increases (by trend analysis) reported for injury (43%), admission (36%), ED use (30% increase overall, 28% for single agents), and exposures (22% increase) were all statistically significantly greater than the increase in the population of US children aged ≤5 years (8%). The 28% rise in in total numbers seen in an ED (14 091 for 2008 vs 2001) was essentially driven by the 60% increase in the number presenting directly to an ED (12 530 for 2008 vs 2001). The number of patients referred from home to an ED by poison centers was statistically unchanged. Looking at the 2 self-ingestion groups (95% of total patients), the OTC medication admission rate was 5.3% for patients for whom the initial poison center contact came from an ED vs 5.3% from those initially calling from home, the OTC medication injury rate was 2.6% vs 2.8%, the prescription medication group admission rate was 18.5% vs 15%, and the prescription medication injury rate was 8.7% vs 5.8%.
Figure 2Pediatric poisoning trends vs population change from 2001 baseline. Visual display shows actual values, see text for linear trend changes.
Table II shows the total impact of each group and medication class on ED visits, admissions, and injuries as well as the associated trends. Only statistically significant changes are reported. The rise in ED evaluations accounted for essentially all the numerical rise in admissions and most of the increase in injuries. Oral hypoglycemic agents accounted for the highest admission rate and the highest injury rate. Prescription opioid analgesics, sedative-hypnotics, and cardiovascular drugs were 3 groups with both a high number of associated total visits and a significant growth in admission rate and/or injury rate.
Table IIChildren ≤5 years seen in an ED following ingestion of a single pharmaceutical product volume admissions injuries
Therapeutic errors with OTC acetaminophen and cough and cold medications were not significant contributors to ED visits (1.2%), admissions (1.2%), or injuries (1.7%). Although small, therapeutic error–related ED visits with acetaminophen did rise 71% during the period with numbers of admissions and injuries up proportionately. In contrast, there was no change in the number of ED evaluations and admissions associated with therapeutic errors due to cough and cold medications, but the rate of injury was down 36% and the number of injuries was down proportionately.
US Drug Enforcement Administration ARCOS data were available for 2000-2007. Trend analysis demonstrates that in the 2000-2007 period, prescriptions for oxycodone increased 182%; hydrocodone, 159%; morphine, 159%; methadone, 559%; and fentanyl, 222%. In contrast, codeine sales declined 24%.
Deaths
Ninety unintentional death cases were listed in the database. Additional information was available for all except 1 case (a self-ingestion of clonidine). That case was included as related to the ingestion. Of these 90 cases, 1 was a duplicate, 1 involved a child in a foreign country, and 12 did not occur via ingestion, and for 10 cases, the mentioned medication did not contribute to the death. The remaining 66 cases are displayed in Table III. The numbers are too small for trend analysis so they are presented in half periods. Eight of these cases involved >1 medication, but only the most contributory medication is listed.
Consistent with injury trends, deaths were most frequently related to unintentional exposure to opioid analgesics and cardiovascular agents. Deaths from therapeutic error related to OTC analgesics only occurred in the first half of the study period. The absence of OTC analgesics in the second half is statistically different (as percentage of total).
Discussion
These poison center data confirm and extend reports from ED injury datasets that numbers of children visiting EDs after medication exposure is increasing.
These data provide additional information on the medications causing the increase and extent of the increasing burden (admissions, morbidity, and mortality). They demonstrate that the largest part of that burden results from children finding and ingesting medication by themselves. The greatest increase is from prescription pharmaceuticals, particularly opioid analgesics, sedative-hypnotics (eg, benzodiazepines, muscle relaxants, and sleep aids), and cardiovascular medications. In contrast, the consequence of children experiencing therapeutic error at home is numerically small and increasing only minimally. The likely causes for these changes suggest that a reemphasis on “poison-proofing” efforts may be a good, but insufficient, strategy. The similarity of the substance type, reason, origin, and outcome distributions of the 67 080 mostly multiple-product exposure patients excluded from the detailed analysis confirms that excluding these patients did not affect the conclusions.
The most likely explanation for these observations is a rise in the number of medications in the environment of small children. Even if there were no decline in the utilization or efficacy of “poison proofing,” more contact with more medications would result in more episodes of prevention failure. In a 1998-1999 survey of medication use, 50% of adults had taken at least 1 prescription medication in the preceding week and 7% had taken ≥5.
The ARCOS data provide evidence that prescriptions for opioid analgesics have increased. This is also the medication group with the single greatest increase in impact—visits are up 101%, the rate of admission is up 86%, and the rate of injury is up 92%.
The 24% rise in the number of visits following self-ingestion of OTC medications (59% for acetaminophen) without a change in the admission or injury rate can be explained only by more medication being available in the home or by less effective home prevention. The increased societal emphasis on pain management may explain some of this if it makes OTC analgesic medications more available in the home, particularly if these medications are viewed as safe.
Data from IMS Health on acetaminophen sales from 2004-2008, presented by the US Food and Drug Administration at a 2009 advisory committee meeting, showed a 28% increase in OTC acetaminophen use in just that portion of our study period.
It is also possible that some types of medications previously less available in the environment of young children have become more available. As obesity and the metabolic syndrome have increased in prevalence and affected younger adults, more homes of small children may have antihypertensive and antidiabetic medicines prescribed for parents or siblings. Data for older children specifically suggests that type 2 antidiabetic medications use has increased.
The increase in the admission rate and severity for certain medications may be related to an increasing use of sustained-release medications and substitution of more potentially toxic medications. As the use of hydrocodone and oxycodone has risen, the use of codeine has fallen. There may be a shift from diuretics and renin-angiotensin system–related agents toward beta blockers and calcium channel antagonists for the treatment of hypertension. One survey of adult medication use found that between 1998-1999 and 2004, metoprolol use increased 471%.
The significant fall in the admission and injury rate for anticonvulsants may illustrate the opposite—a shift to less sedating anticonvulsants.
In addition to more medications being available and more medications that are toxic to a toddler in a single adult dose, access to medications may also have increased. Effective efforts at “poison proofing” may have plateaued or declined for all groups. Improvement science suggests that self-generated behavioral approaches at best can achieve only first order reliability—that is, the target behavior is performed about 90% of the time. All medication users find it inconvenient to store medication in locked cabinets, particularly medications that are used once or several times daily. They may not understand the life-threatening impact of some medications in just 1 dose, discount the potential toxicity of OTC medications, or underestimate the likelihood that it will happen in their home with their children. In addition, almost all medication users at one time or another must take their medication while away from home. Data suggest consumers treat different classes of hazardous products differently and medications in use differently.
The risk perception behind these choices and the choices themselves point to the limits of behavior based prevention approaches.
In the same home, it is possible that the per-prescription “exposure rate” for siblings’ medications may exceed that for parents’ medications, but published data on “whose medicine” is limited and not present in this database. Grandparents’ medications are estimated to be involved in 10%-20% of exposures.
“Hang up your pocketbook”—an easy intervention for the granny syndrome: grandparents as a risk factor in unintentional pediatric exposures to pharmaceuticals.
“Hang up your pocketbook”—an easy intervention for the granny syndrome: grandparents as a risk factor in unintentional pediatric exposures to pharmaceuticals.
That may be relevant to interventions, but these data do not allow an evaluation of that possibility.
Given the 22% increase in pediatric pharmaceutical–related calls to poison centers, including those not referred to EDs, without any statistical change in the number of young children referred to EDs, it is unlikely that the rise in visits is a failure on the part of poison centers. In fact, these data suggest poison centers have significantly reduced the referral of lower-risk patients to maintain the same total number of referrals. The apparent similarity of admission rates and injury rates between those referred by a poison center and those presenting directly to an ED likely reflects referral bias—that relatively fewer low-risk directly presenting exposed children are reported to poison centers by hospitals. If so, increased poison center use from home could prevent some ED visits.
For this study, OTC antihistamines were not classified by use—allergy (where less toxic, nonsedation agents may substitute) vs sleep aids—or by subclass (sedating or nonsedating). It is possible that the antihistamines contributing most to resource use, morbidity, and mortality are be those used as sleep aids and thus a part of society’s increasing use of sedating medications.
Misdosing of acetaminophen has been a Food and Drug Administration focus through the study period.
Acetaminophen-related deaths in 2001-2004 were all from therapeutic errors. Given the rise in visits following acetaminophen-related therapeutic errors, the absence of death suggests a lower degree of overdosing and/or earlier consideration of risk and initiation of treatment by physicians. The drop in therapy-related cough and cold product injuries is not explained by a change in use because injuries dropped 36% even when visits rose 8%.
Dosing information on pediatric OTC products has received recent academic and public attention.
The results of this study suggest that focus should shift to self-ingestion and prescription products. Going forward, there may be some additional gains from attention to preventing therapeutic acetaminophen errors but the largest potential benefits would come from a shift in attention to packaging design changes that reduce the quantity a child could quickly and easily access in a self-ingestion episode (eg, flow restrictors on liquids, one-at-a time tablet-dispensing containers) without impairing appropriate use at other times. Such changes should be applied to both adult and pediatric products and to OTC and prescription products.
The limitations of this study are apparent in the required disclaimer from the AAPCC (see funding and conflict of interest information on title page). Most notably, the passive nature of the database may make it an incomplete count of cases, an underestimate. However, these data match those of the Consumer Product Safety Commission’s National Electronic Injury Surveillance System in volume and substance distribution.
Those data are collected via an entirely different mechanism, by ED sampling. This corroborates the data independently and suggests the observations are not simply a shift in the pattern of poison center use by parents/physicians. Furthermore, even if both datasets represent underestimates of the problem, the nature of the important agents and trends over time should be valid. If there is any direction of bias from incomplete reporting, patients not called to a poison center by emergency personnel are likely to have been less ill and may explain part of the admission rate of directly presenting patients. In addition, because case information is reported to poison centers by telephone in follow-up calls, not all data on every case is communicated from the hospital or entered into the database. Incompletely reported observations about reported patients could only underestimate the severity of the problem, again biasing toward less severity. It is also possible that with 500 000 direct data entry electronic records, some of the data have been entered incorrectly. Data have been entered at 61 locations by hundreds of people over 8 years, but there is no obvious systematic component to data entry errors.
We conclude that the problem of pediatric medication poisoning is getting worse, not better. Past preventive efforts have proved to be inadequate. More children are exposed, more are seen in an ED, more are admitted, and more are injured each year. The greatest increases in all these variables have been from prescription pharmaceuticals, particularly opioid analgesics, sedative-hypnotics, and cardiovascular medications. New efforts must be directed at these most consequential circumstances. Educational efforts are important but are unlikely to make a significant improvement alone. Education interventions should readdress home storage of all medications, repackaging of medications—particularly grandparents’ medications in “pill minders,” and the fact that older siblings may not be as careful as parents when opening containers or taking medications. Storage devices and child-resistant closures may need to improve. Additionally, mechanical barriers to ingestion such as blister packs may be required for more substances. Preventive efforts should also address appropriate prescribing and society’s problem with opioid and sedative abuse.
The authors would like to thank Fred Henretig, MD (Children’s Hospital of Philadelphia), for his manuscript review and Ben Kerrey, MD (Cincinnati Children’s Hospital Medical Center), for manuscript review and assistance with Figure 1.
Appendix
Table IED visits by children ≤5 years following ingestion of a single pharmaceutical product from AAPCC NPDS 2001-2008
NPDS Annual Reports of the American Association of Poison Control Centers 1990-2008. Available from http://www.aapcc.org/dnn/NPDSPoisonData/NPDSAnnualReports.aspxAccessed on May 24, 2010. (For 2006-2008, the classic version of Table 22 of the report was obtained from the AAPCC.)
National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, WISQARS Nonfatal Injury Reports. Available from http://webappa.cdc.gov/sasweb/ncipc/nfirates2001.html. Accessed October 18, 2010.
“Hang up your pocketbook”—an easy intervention for the granny syndrome: grandparents as a risk factor in unintentional pediatric exposures to pharmaceuticals.
The American Association of Poison Control Centers (AAPCC; http://www.aapcc.org) maintains the national database of information logged by the country’s 61 Poison Control Centers (PCCs). Case records in this database are from self-reported calls: they reflect only information provided when the public or healthcare professionals report an actual or potential exposure to a substance (eg, an ingestion, inhalation, topical exposure, etc) or request information/educational materials. Exposures do not necessarily represent a poisoning or overdose. The AAPCC is not able to completely verify the accuracy of every report made to member centers. Additional exposures may go unreported to PCCs and data referenced from the AAPCC should not be construed to represent the complete incidence of national exposures to any substance(s). The authors’ opinions do not necessarily represent those of the AAPCC or its member centers.
The dramatic reduction in pediatric deaths from unintentional poisonings in the last half of the 20th century is a model of the successful application of injury prevention theory and practice. The increases in hospitalizations, emergency department (ED) visits, and persistence of deaths caused by unintentional pediatric pharmaceutical poisonings in the first decade of this century are described by Bond et al1 in this issue of The Journal and remind us that this effort is not yet complete. Hopefully the findings in this study can help catalyze targeted efforts to reverse the rise in injuries from pediatric pharmaceutical poisonings and push the number of pediatric deaths closer to zero.
In the article, “The Growing Impact of Pediatric Pharmaceutical Poisoning,” by Bond et al, J Pediatr 2012;160:265-70, the authors submitted incorrect versions of Tables I and II for publication. The corrected versions of Tables I and II are below. Additionally, the number of significant injuries listed in the Abstract and Results section should be 18 192 (not 18 191).
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