Clinical Toxicology (2014), 52, 880–888 Copyright © 2014 Informa Healthcare USA, Inc. ISSN: 1556-3650 print / 1556-9519 online DOI: 10.3109/15563650.2014.953168
POISON CENTRE
Medication errors reported to U.S. Poison Control Centers, 2000–2012 T. J. BROPHY,1,2 H. A. SPILLER,1,3 M. J. CASAVANT,1,3 T. CHOUNTHIRATH,2 M. D. SMITH,2 and H. XIANG1,2 1The
Ohio State University College of Medicine, Columbus, OH, USA for Injury Research and Policy at the Research Institute of Nationwide Children’s Hospital, Columbus, OH, USA 3Central Ohio Poison Center, Columbus, OH, USA Clinical Toxicology Downloaded from informahealthcare.com by University of Otago on 09/11/14 For personal use only.
2Center
Context. Previous studies of medication errors have largely focused on healthcare facilities and have not reported generalizable national trends among out-of-hospital medication errors. Objective. We sought to understand U.S. trends in medication errors, including the agerelated risks, the involved medications, and the medical outcomes. Materials and methods. We performed a retrospective analysis of National Poison Data System (NPDS) data from the American Association of Poison Control Centers for years 2000–2012. Medication error cases were analyzed by age, gender, pharmaceutical involved, substance rank, dosing error type, management site, level of healthcare received, and medical outcome. Trends in medication error rates were analyzed using Poisson regression. Results. From 2000 to 2012, the NPDS recorded 2,913,924 calls reporting unintentional pharmaceutical-related errors that met inclusion criteria. Non-healthcare facility calls comprised 99.2% calls related to unintentional therapeutic errors. Eighty-seven percent of medication errors were managed on site. The annual medication error rate for all callers per 10,000 U.S. population increased significantly (p ⬍ 0.0001) by 69.8% from 2000 (4.98 calls per 10,000 population) to 2012 (8.46 calls per 10,000 population). Among adults aged 20 years and older, age was positively correlating (r ⫽ 0.96) with the rate of medication error. Analgesics were the most frequent pharmaceutical class involved in medication errors for ages 6–49 (N ⫽ 221,061). Among ages 20–49 years, opioid-related medication errors decreased by 7.9% from 2010 to 2012. Cardiovascular drugs were the leading source of injury among all ages (N ⫽ 14,440) and also the leading pharmaceutical class involved in medication errors among adults 50 years and older (N ⫽ 187,760). Conclusion. Medication errors continue to be a source of preventable injury with increasing incidence across the out-of-hospital population. Keywords Poison Control Centers; Unintentional therapeutic errors; Analgesics; Cardiovascular drugs
per week.6 Previous research regarding out-of-hospital medication errors was limited to state-wide studies, at-risk populations, or specific medications, limiting the generalizability of results to the entire population.7–9 In 2006, a 6-year retrospective analysis utilizing national poison control center data described out-of-hospital medication errors, indicating high frequencies of errors involving analgesics, cardiovascular agents, and cold and cough medications.10 However, this 2006 study was limited to simple counts of error scenario characteristics and did not provide information regarding temporal patterns or age associations.
Introduction Background Medication errors are a significant source of preventable mortality and healthcare costs, as detailed in the Institute of Medicine’s seminal report.1 A 2005 study estimated that adverse drug events leading to outpatient treatment increased from 2.9 million to 4.3 million from 1995 to 2001.2 In healthcare facilities, electronic medication dispensing systems have proven to be an effective intervention to reduce medication errors.3 In the outpatient setting, interventions for the pediatric population have dramatically decreased cold and cough medication errors.4,5
Goals of this investigation We analyzed call data from the National Poison Data System (NPDS) of the American Association of Poison Control Centers (AAPCC). Due to its standardized data collection, large sample size, and near real-time data, the NPDS is well-suited for medication error surveillance. The goal of our study is to characterize the trends of medication errors, including the age-related risks and the medications involved.
Importance Studies of medication errors for all ages are warranted, given that 82% of U.S. adults take at least one medication Received 12 March 2014; accepted 4 August 2014. Address correspondence to Huiyun Xiang, MD, MPH, PhD, Center for Injury Research and Policy, The Research Institute at Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, USA. Tel: ⫹ 614-355-5850. E-mail: [email protected]
880
Medication errors 881
Methods
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Study design and setting This study was a 13-year retrospective analysis of data from the NPDS. The NPDS is a proprietary database maintained by the AAPCC. The NPDS collects data in near real-time for every call to the nation’s regional poison centers, which serve the entire population of the U.S. and its territories.11 This study was reviewed by the IRB of the authors’ institution and judged to be exempt. Selection of participants NPDS data were requested for all “unintentional therapeutic error” calls from January 1, 2000 to December 31, 2012 involving pharmaceutical substances as determined by the AAPCC generic substance coding system, which is maintained by Micromedex POISINDEX ® Managements.11,12 In NPDS, an unintentional therapeutic error is defined as “an unintentional deviation from a proper therapeutic regimen that results in the wrong dose, incorrect route of administration, administration to the wrong person, or administration of the wrong substance”. Drug interactions resulting from unintentional administration of drugs or foods which are known to interact are also included.11 Only exposures to medications or products used as medications are included in our study. Specifically excluded were pediatric exploratory ingestions, intentional drug misuse and drug abuse, and suicidal or malicious drug exposures. Additionally, calls were limited geographically to the 50 United States and District of Columbia so that trend analysis could be conducted using available U.S. population data. In this report, the terms “unintentional therapeutic error” and “medication error” are used interchangeably. The AAPCC records separate exposure data for each pharmaceutical reported in calls involving multiple substances, resulting in the number of medication error exposures exceeding the total number of calls. Because the majority of poison center calls are self-reported, without healthcare personnel involvement, the term “call” or “caller” refers to an individual experiencing a medication error. In this report, the term “exposure” refers to each separate pharmaceutical reported for a given caller. For calls with multiple pharmaceuticals reported, data analyses were limited to only the pharmaceutical with the greatest contribution to any clinical effects as determined by the poison center specialist managing the call, denoted by substance rank. Unless noted otherwise, our analysis focused on individual callers and the principal pharmaceutical determined by the poison center specialist. Methods and measurements Data were analyzed by subject’s age, gender, involved pharmaceuticals, substance rank, dosing error type, management site, level of healthcare received, and medical outcome. Pharmaceuticals were classified according to the NPDS generic coding system and by consulting a FDA drug database.13 Under AAPCC pharmaceutical coding, the analgesic Copyright © Informa Healthcare USA, Inc. 2014
category encompasses prescription medications, including opioids, and non-prescription analgesics, such as non-steroidal anti-inflammatory drugs (NSAIDs). In this study, opioid pharmaceuticals include opioids and any opioid combination pharmaceuticals; acetaminophen (paracetamol) drugs include acetaminophen and any non-opioid acetaminophen combination pharmaceuticals; and NSAIDs include NSAIDs and any non-opioid, non-acetaminophen combination NSAIDs. Cold and cough preparations include combination pharmaceutical products, such as antihistamine and/or decongestant products with analgesics. Hormone-based pharmaceuticals include medications such as insulin, oral hypoglycemics, thyroid preparations, and steroids. Medical outcomes and dosing error scenarios were classified by poison center specialists according to standard NPDS definitions.11 In this study, injury was defined as any medication error causing a medical outcome coded as moderate effect, major effect, or death. Similar to the NPDS Annual Report, children were defined as less than 20 years of age, with age subgroups of 0–5 years, 6–12 years, and 13–19 years. Adults were defined as aged 20 years and older, with age subgroups by decade of life and the most senior age group as 80 years and older.11 Analysis NPDS data were analyzed using SAS 9.3 (SAS Institute, Inc., Cary, NC). Most data analysis was descriptive in nature and limited to event frequencies for the variables under study. U.S. Census Bureau July 1 intercensal and postcensal resident population estimates for 2000 through 2012 were used as the denominator for the overall and age-specific medication error rate calculations.14,15 Analysis was performed by the stated age groups, with results displaying combined age groups when similar trends were observed. Pearson correlation analysis was used to evaluate the correlations between age and the medication error rate, the percentage of injuries, and the percentage of multiple-substance errors. The Pearson product-moment correlation coefficient was represented by r. To investigate the overall and age group-specific trends in the annual rate of medication error calls, Poisson models were fit to the data with year as the independent variable. We used the Pearson method to estimate a scale parameter when there was evidence of overdispersion (greater variability than expected with the given model). Significant trends in the annual rate of calls are reported as the percentage changed with a p-value from the Poisson regression. All statistical significance was established at the two-tailed significance level of α ⫽ 0.05.
Results Study population From 2000 through 2012, the NPDS recorded 2,980,042 calls reporting pharmaceutical-related unintentional therapeutic errors, of which 2,913,924 calls (97.8%) met the inclusion criteria (Table 1). Calls were excluded if: (1) the events were confirmed non-exposures (4,479 cases), (2) the pharmaceuticals were unrelated to the clinical effects (53,748
882 T. J. Brophy et al. Table 1. Total number of medication errors by pharmaceutical class for all ages, years 2000–2012. Single-substance medication error calls
Injuries†
Calls
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Pharmaceutical class Analgesics Cold and cough preparations Cardiovascular drugs Antihistamines Antimicrobials Hormones and hormone antagonists Antidepressants Sedatives, Hypnotics, Antipsychotics Gastrointestinal preparations Anticonvulsants Stimulants Asthma therapies Vitamins Anticholinergic drugs Eye, Ear, Nose, and Throat Preparations Miscellaneous drugs Topical preparations Electrolytes and minerals Muscle relaxants Diuretics Anticoagulants Dietary Supplements, Herbals, Homeopathics Anesthetics Veterinary drugs Unknown drug Serums, Toxoids, Vaccines Antineoplastics Diagnostic agents Narcotic antagonists Radiopharmaceuticals Total
All medication error calls*
Injuries†
Calls
Change in no. of calls, 2000–2012‡
N
%
N
%
N
%
N
%
%
469322 316807 226882 221654 220274 151321 118791 110924 83864 74325 72029 62999 56611 54221 51512 49598 37076 23712 22336 18536 17955 16783 9342 9087 8189 7182 6509 1980 382 34 2520237
18.6 12.6 9.0 8.8 8.7 6.0 4.7 4.4 3.3 3.0 2.9 2.5 2.3 2.2 2.0 2.0 1.5 0.9 0.9 0.7 0.7 0.7 0.4 0.4 0.3 0.3 0.3 0.1 0.0 0.0
6450 2855 9430 1440 1659 6157 4641 5318 1297 3596 2504 1506 237 284 1446 1624 650 383 1118 389 563 404 559 81 269 68 265 142 61 5 55401
11.6 5.2 17.0 2.6 3.0 11.1 8.4 9.6 2.3 6.5 4.5 2.7 0.4 0.5 2.6 2.9 1.2 0.7 2.0 0.7 1.0 0.7 1.0 0.1 0.5 0.1 0.5 0.3 0.1 0.0
534874 369711 306091 249079 229547 171094 145918 138338 90377 100734 83731 67812 59818 55564 52627 60395 37475 25636 26415 23003 22446 18011 9688 9368 8734 7861 7052 2014 471 40 2913924
18.4 12.7 10.5 8.6 7.9 5.9 5.0 4.8 3.1 3.5 2.9 2.3 2.1 1.9 1.8 2.1 1.3 0.9 0.9 0.8 0.8 0.6 0.3 0.3 0.3 0.3 0.2 0.1 0.0 0.0
8410 3481 14440 1705 1827 7558 5907 6871 1491 4634 2911 1623 269 366 1472 2119 671 426 1421 511 681 455 609 87 299 79 282 146 78 5 70834
11.9 4.9 20.4 2.4 2.6 10.7 8.3 9.7 2.1 6.5 4.1 2.3 0.4 0.5 2.1 3.0 0.9 0.6 2.0 0.7 1.0 0.6 0.9 0.1 0.4 0.1 0.4 0.2 0.1 0.0
91.9 ⫺ 31.2 126.4 133.6 79.3 192.0 76.8 129.6 97.6 105.8 139.7 19.7 95.2 3206.7 66.9 217.3 98.6 95.7 98.7 91.2 316.8 338.4 49.9 66.5 149.1 136.6 239.2 34.2 338.5 200.0
*All Medication Error Calls includes single-substance and multiple-substance exposure calls. Multiple-substance calls are categorized according to the primary pharmaceutical responsible for clinical effects, as determined by the poison control specialist. †Injuries include all medical outcomes coded as moderate effect, major effect, or death. ‡Percent change in the number of calls from 2000 to 2012 is calculated as the overall percent change in the number of calls received for each pharmaceutical class.
cases), or (3) the case occurred outside the 50 United States or District of Columbia (7,891 cases). All single-substance (86.5%) and multiple-substance calls (13.5%) were included in this study. Non-healthcare facility calls comprised 99.2% of study calls. Overview Children under 20 years of age were involved in 47.3% of all medication errors reported, with children younger than 6 years involved in 27.4% of all medication errors. More than half (55.8%) of medication errors among children involved males. More than two-thirds 67.9% of all adult (ⱖ 20 years of age) medication errors involved females. The most common dosing error within each age group was inadvertently taking medication twice, attributed to 31.8% of all calls. Among the 70,834 medication error injuries, moderate clinical effect (N ⫽ 65,825) was much more common than major clinical effect (N ⫽ 4,495) or death (N ⫽ 514). Eighty-seven percent
of all medication error calls were able to be managed on site, not at a healthcare facility. Among the 240,851 (8.3%) callers that received healthcare facility treatment, most were treated and released (77.4%), with the remaining patients being admitted to non-critical care units (12.2%), critical care units (9.6%), or psychiatric units (0.7%). The rate of healthcare facility use per 100,000 population increased significantly (p ⬍ 0.0001) by 104.1% from 3.86 calls in 2000 to 7.87 calls in 2012. Medication errors by age group The annual medication error rate for all callers per 10,000 U.S. population increased significantly (p ⬍ 0.0001) by 69.8% from 4.98 calls in 2000 to 8.46 calls in 2012. A linear trend was observed across all age groups, except children 0–5 years old, in which the direction of the trend changed. Among children, the rate of medication errors decreased as age increased (r ⫽ ⫺ 0.97). Children under 6 years old Clinical Toxicology vol. 52 no. 8 2014
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Medication errors 883 (25.76 calls per 10,000 population) had over twice the rate of medication errors as children ages 6–12 years (10.45 calls per 10,000) and five times the rate for ages 13–19 years (4.85 calls per 10,000 population). The annual medication error rates among children under 6 years increased significantly by 45.7% (p ⬍ 0.0001) from 2000 to 2005 followed by a significant decrease of 11.5% (p ⬍ 0.0001) from 2005 to 2010.. The annual medication error rates increased significantly by 72.0% (p ⬍ 0.0001) for children 6–12 years old and 67.3% (p ⬍ 0.0001) for teenagers 13–19 years old. The annual medication error rates peaked in 2009 for both 6- to 12-year olds (12.64 calls per 10,000 population) and 13- to 19-year olds (5.72 calls per 10,000 population). Among adults, age of the population was positively correlated (r ⫽ 0.96) with the rate of a medication error, with significant (p ⬍ 0.0001) linear increases in annual medication error rates observed in all age groups from 2000 to 2012 (Fig. 1). All adult age groups reached a peak medication error rate in 2011, with maximum rates ranging from 4.00 (ages 20–29 years) to 12.86 (ages ⱖ 80 years) calls per 10,000 population. Age of the population was also positively correlated (r ⫽ 0.90) with the percentage of injuries and positively correlated (r ⫽ 0.92) with the percentage of multiple-substance errors, ranging from 15.2% in 20- to 29-year olds to 23.9% in adults 80 years and older. Medication errors by pharmaceutical class Among all medication errors, the most frequently involved pharmaceutical classes were analgesics, cold and cough preparations, and cardiovascular drugs (Table 1). During the study period, the annual number of cardiovascular and analgesic medication errors increased by 126.4% and 91.9%, respectively. Cold and cough preparations were the only class observed to decrease (⫺ 31.2%) in the annual number of errors. Anticholinergic drugs had the greatest percent increase (3206.7%) in the number of error calls from 2000 (240 calls) to 2012 (7,936 calls). Among all medication error injuries, 20.4% involved cardiovascular drugs, 11.9%
involved analgesics, and 10.7% involved hormone-based pharmaceuticals. Analgesic medication errors were among the top three most frequently reported pharmaceutical classes for every age group (Table 2). Among children under 6 years old, the majority of medication errors were once due to cold and cough preparations; however, cold and cough preparation errors showed a dramatic decrease after 2006 and analgesics became the leading medication involved in errors from 2008 to 2012 (Fig. 2). Analgesics were the leading pharmaceutical class involved in medication errors within each age group from 6 to 49 years old, accounting for 18.8% of calls (N ⫽ 221,061) in this age range. Among adults over 50 years, analgesics were the second most reported medication class (N ⫽ 90,841, 11.8%). Across all ages, opioids accounted for 54.9% (N ⫽ 4,616) of all injuries due to analgesics, with fewer injuries being reported for acetaminophen-based drugs (N ⫽ 2,225) or NSAIDs (N ⫽ 1,506). Of all opioid medication error calls, 3.7% resulted in an injury, as compared to injuries documented in 1.1% of acetaminophen-based error calls and 0.7% of NSAID error calls. A subanalysis was performed to characterize the agerelated trends by analgesic subclass. Due to similarities in trends among age groups, the results are presented by ages under 20 years old (children), ages 20–49 years old, and ages 50 and older. Among children, acetaminophen-based drugs accounted for 46.4% of medication errors (N ⫽ 138,361), followed by NSAIDs (N ⫽ 130,232, 43.7%) and opioids (N ⫽ 29,293, 9.8%; Fig. 3). For adults aged 20–49 years, opioids were the leading class of analgesics involved in medication errors (N ⫽ 43,869, 36.7%), followed by NSAIDs (N ⫽ 42,667, 35.7%) and acetaminophen-based drugs (N ⫽ 32,371, 27.1%; Fig. 4). Although opioids increased 88.1% in annual medication error frequency from 2000 to 2012, opioid medication errors decreased 7.9% from 2010 to 2012. Hydrocodone/acetaminophen was the leading opioid involved in medication errors for ages 20–49 years old, accounting for 30.4% (N ⫽ 13,337) of opioid medication errors and paralleling the overall opioid decline by decreasing
Fig. 1. Rate of medication error calls per year for adults, ages ⱖ 20 years. Copyright © Informa Healthcare USA, Inc. 2014
Antimicrobials (5.6%) Antidepressants (5.7%) Sedatives, Hypnotics, Antipsychotics (8.1%)
Anticholinergic Drugs (7.5%) Antimicrobials (5.7%) Hormone-based Pharmaceuticals (8.2%)
Antimicrobials (6.2%)
Sedatives, Hypnotics, Antipsychotics (6.4%)
Antimicrobials (7.8%) Antihistamines (8.0%)
Asthma Therapies (4.5%) 5
Gastrointestinal Preparations (4.0%)
Antimicrobials (6.6%)
Cold and Cough Preparations (11.3%) Cardiovascular Drugs (9.2%) Stimulants (8.6%) Antihistamines (10.6%) 4
Cold and Cough Preparations (12.2%)
Antidepressants (9.1%) Stimulants (11.9%) Antihistamines (12.4%) Antimicrobials (11.3%) 3
Antimicrobials (12.3%)
Analgesics (15.2%) Analgesics (18.3%) Analgesics (21.2%) 2
Antihistamines (18.2%)
Stimulants (10.2%)
Cold and Cough Preparations (9.5%) Antidepressants (8.6%)
Antihistamines (7.6%)
Cold and Cough Preparations (9.0%) Sedatives, Hypnotics, Antipsychotics (7.3%)
Analgesics (11.0%) Hormone-based Pharmaceuticals (9.3%) Antidepressants (8.8%) Cardiovascular Drugs (10.6%)
Sedatives, Hypnotics, Antipsychotics (7.7%) Cold and Cough Preparations (7.7%)
Hormone-based Pharmaceuticals (12.1%) Analgesics (12.7%) Cardiovascular Drugs (11.0%) Antidepressants (11.3%)
Cold and Cough Preparations (14.2%) Antidepressants (9.5%) Antihistamines (11.3%)
Antidepressants (9.4%)
Cardiovascular Drugs (22.9%) Cardiovascular Drugs (27.5%) Analgesics (17.8%) Analgesics (18.7%) Analgesics (23.4%) Analgesics (23.1%) Antihistamines (16.1%) Cold and Cough Preparations (20.9%) Analgesics (32.2%) Cold and Cough Preparations (34.7%) 1
2000 2012 2000 2012 2000
Cold and Cough Preparations (20.8%) Analgesics (20.6%)
Analgesics (18.1%)
2000 2012 2000 2012
Age 20–29 Age 13–19 Age 6–12 Age 0–5 Pharmaceutical class rank
Table 2. Most frequently reported pharmaceutical classes in medication errors as a percent of age group total errors in 2000 and 2012.
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Age 30–49
2012
2000
Age ⬎ 50
2012
884 T. J. Brophy et al. 9.7% from 2010 (N ⫽ 1,310) to 2012 (N ⫽ 1,183). After 2009, there was also decreasing number of calls related to acetaminophen medication errors among adults, 20–49 years of age. Among adults aged 50 years and over, opioids represented 44.5% (N ⫽ 40,419) of analgesic errors, with lower percentages of NSAID (N ⫽ 30,619, 33.7%) and acetaminophenbased (N ⫽ 19,229, 21.2%) medication errors (Fig. 5). Cardiovascular medications were the most frequently reported medication error among adults aged 50 years or older (N ⫽ 187,760, 24.3%). However, cardiovascular medication errors were also the second most frequently reported medication class among ages 30–49 years (N ⫽ 44,078), with an increasing trend from 2000 (N ⫽ 2,350) to 2012 (N ⫽ 4,128; Table 2). A subanalysis of cardiovascular medication errors in adults aged 50 years or older was performed to describe the contributing agents (Fig. 6). The annual frequency of cardiovascular medication errors in adults aged 50 years and older increased 133.8% from 2000 (N ⫽ 8,138) to 2012 (N ⫽ 19,027). Beta blockers were the leading cardiovascular drug subclass involved in medication error calls (N ⫽ 50,670, 27.0%), followed by calcium antagonists (N ⫽ 36,480, 19.4%), angiotensin-converting enzyme (ACE) inhibitors (N ⫽ 25,739, 13.7%), antihyperlipidemics (N ⫽ 20,212, 10.8%), and angiotensin receptor blockers (N ⫽ 17,884, 9.5%). Among the 9,598 injuries related to cardiovascular medications among adults aged 50 years or older, beta blockers accounted for 29.1% of these injuries and calcium antagonists accounted for 28.0%.
Discussion This study provided an overview of trends in medication errors over a 13-year period in the U.S. Among all age groups except children under 6 years, the annual rate of medication errors has increased significantly from 2000 to 2012. The number of medication errors reported to poison control centers highlights the extent of the problem, affecting all ages and nearly all pharmaceuticals. The vast majority of medication errors do not result in injury, and very few of these injuries result in major clinical effects or deaths, which emphasizes that healthcare treatment is often not necessary. During the study period, over 2.5 million individuals (87.2% of callers) that experienced a medication error were able to be managed on site, typically at home, without further medical treatment. Although this study did not evaluate what proportion of these callers would have sought medical treatment otherwise, the poison control center system has been estimated previously to save between $310 million to $900 million annually from decreased utilization of other healthcare providers.16–18 The aging of the U.S. population is an important factor that will likely only exacerbate current trends in medication errors. Increasing age has been associated previously with increasing rates of medication use and polypharmacy.6,19 Our results show that among adults 20 years or older, as age increased so did the rate of medication errors, the percentage of multiple-substance errors, and the proportion injured. Clinical Toxicology vol. 52 no. 8 2014
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Medication errors 885
Fig. 2. Number of medication error calls by pharmaceutical class, ages ⬍ 6 years.
Although there have been studies regarding successful interventions to reduce polypharmacy among older adults,20–24 our findings suggest that medication errors continue to occur at increasing rates in this population. There was a significant decrease in the annual rate of unintentional medication errors among children under 6 years old from 2005 to 2012. This decrease was mainly driven by the decrease in the annual number of cold and cough medication errors (Fig. 2), which coincided with the concerted efforts to restrict cold and cough medicine use in this age group by the Food and Drug Administration (FDA) and the voluntary removal of products marketed for very young children as well as voluntary label changes by the Consumer Healthcare Products Association (CHPA).4,5,25 Despite the dramatic decline seen in cold and cough medication errors, analgesic and antihistamine medication errors continued to increase (Fig. 2). It is possible that the decrease in availability of cold and cough preparations in the home for this age group has led to the increased use of analgesics and antihistamines, but further study is needed. Analgesics were the leading class of medication errors in each age group from 6 to 49 years old, with the annual
frequency of analgesic medication errors increasing in all age groups from 2000 to 2012. In adults aged 20–49 years, opioid medications were the most frequently reported analgesic medication errors, increasing 88.1% from 2000 to 2012. The increase in opioid medication errors is not unexpected, as the documented increase in the per capita sales of opioid medications has been correlated to increases in unintentional overdoses and deaths.26,27 However, after steadily increasing from 2000 to 2010, the number of opioid medication errors in ages 20–49 decreased by nearly 8% from 2010 to 2012, despite the annual call rate remaining relatively constant among these age groups during this time (Fig. 1). It is possible that this change in opioid trend may be linked to the considerable efforts at both the state and federal levels to implement the prescription drug monitoring programs (PDMPs) and related legislation. Previous studies have shown the potential impact of PDMPs on the mitigation of opioid abuse and misuse.28 However, there have been mixed findings as to whether PDMPs have been linked to decreased opioid use.29,30 Alternatively, it is possible that PDMPs might have impacted physician behavior, leading to more judicious opioid prescribing practices.31 Lastly, the focus on rising
Fig. 3. Number of analgesic medication error calls by subclass, ages ⬍ 20 years. Copyright © Informa Healthcare USA, Inc. 2014
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886 T. J. Brophy et al.
Fig. 4. Number of analgesic medication error calls by subclass, ages 20–49 years.
opioid overdose trends by news media outlets and governmental agencies might have elevated social awareness of opioid use, leading to decreased frequencies of medication errors. As more states fully implement PDMPs, future studies should address their efficacy to reduce not only abuse and intentional misuse, but also unintentional errors. Acetaminophen (non-opioid) calls among 20- to 49-year olds also showed declines after 2009, perhaps related to FDA required label changes in 2009 for over the counter pain relievers and fever reducers.32 Further consideration of this trend and trends in acetaminophen overdose-related emergency department visits and hospitalizations are merited.33 Cardiovascular drugs were a major source of medication errors throughout the study, responsible for the most medication errors in adults 50 years and older and the third most errors for all ages. Of great importance is the observation that although cardiovascular drugs accounted for 10.5% of calls in this study, they were responsible for 20.4% of all injuries due to medication errors. Previous studies have highlighted the impact of cardiovascular drugs in specific populations, such as adults aged 65 years and older or patients at hospitals and nursing homes.34–36
However, our study also found a significant increase in cardiovascular medication errors in adults 30–49 years old. The subanalysis of cardiovascular agents showed the relative number of medication errors by specific subclasses. Although reportedly used less frequently than antihyperlipidemics, beta blockers and calcium channel antagonists showed higher frequencies of medication errors.6 Because beta blockers and calcium channel antagonists can be used as both antihypertensive agents and antiarrhythmic agents, patient confusion about their function may increase their involvement in medication errors. Furthermore, the potential serious side effects of their inappropriate use may cause them to be recognized and reported more frequently in comparison to other medications. Due to the association of obesity with cardiovascular disease, as the prevalence of obesity remains high and continues to affect younger patients,37 treatment with cardiovascular drugs will likely increase. Therefore, future studies regarding medication errors involving cardiovascular agents must correspondingly expand their study population to include middle-aged adults so that the complete study population is considered and appropriate interventions can be designed.
Fig. 5. Number of analgesic medication error calls by subclass, ages ⱖ 50 years. Clinical Toxicology vol. 52 no. 8 2014
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Medication errors 887
Fig. 6. Number of cardiovascular medication error calls by subclass, ages ⱖ 50 years.
Although interventions to reduce medication errors in the hospital setting have been studied and shown effective in recent years, less information is available on ambulatory interventions to prevent medication errors. Medication selfcare educational programs and medication reconciliation have previously been proposed as strategies to reduce outof-hospital medication errors; however, other strategies to prevent errors in the ambulatory population have not been well-studied.38 Further research should address the causes of medication errors so that specific interventions can be designed. There are a number of limitations in this study, including the inherent limitations of retrospective studies and the voluntary nature of reporting medication errors. Another limitation is that our study likely underestimated the true prevalence of medication errors, as many individuals might have made errors without recognition or sought information from online resources. Injury may also be underestimated, as 2.2% of medical outcomes were potentially toxic but unable to be followed. Additionally, because we do not know the daily number of medications taken by each patient, we cannot take this into account as a confounding factor in the correlation analysis between caller age, multiple-substance errors, and injury. Nevertheless, observation of these trends helps to further illustrate the scope of the problem and identify areas of future research. Finally, there was also the potential for error in multiple-substance calls when assigning the drug most responsible for clinical effects. However, as 86.5% of calls were single-substance reports and as there have been no reported systemic biases in the NPDS recording system, the error of assigning the most responsible drug was likely very small.
Conclusions The NPDS provides a large, accessible database conducive to characterizing medication error trends in the out-of-hospital population. From 2000 to 2012, the medication error rate increased significantly among all age groups except for Copyright © Informa Healthcare USA, Inc. 2014
children under 6 years. Among adults aged 20 years or older, the error rate increased with increasing age. Furthermore, analgesics accounted for the greatest number of medication errors in young and middle-aged adults, but adults 50 years and older most frequently reported cardiovascular medication errors. Cardiovascular drugs were the leading source of injury for all age groups.
Disclaimer The American Association of Poison Control Centers (AAPCC; http://www.aapcc.org/) maintains the national database of information logged by the country’s regional poison centers (PCs). 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 (e.g., an ingestion, inhalation, or 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 PCs and data referenced from the AAPCC should not be construed to represent the complete incidence of national exposures to any substance(s).
Acknowledgements Krista Kurz Wheeler is acknowledged for her assistance in revising and editing this manuscript.
Declaration of interest This study was funded in part by the Barnes Medical Student Research Scholarship of The Ohio State University College of Medicine. Efforts of Thiphalak Chounthirath and Dr. Huiyun Xiang were funded by a research grant from the National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, US Department of
888 T. J. Brophy et al. Health and Human Services (Grant #:1R49 CE002106; PI: Dr. Huiyun Xiang). The views expressed here are those of the authors and do not necessarily reflect the official views of the Centers for Disease Control and Prevention.
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References 1. To Err is Human: Building a Better Healthcare System. Washington, DC: Institute of Medicine, Committee on Quality of Health Care in America; 1999. 2. Zhan C, Arispe I, Kelley E, Ding T, Burt CW, Shinogle J, Stryer D. Ambulatory care visits for treating adverse drug effects in the United States, 1995–2001. Jt Comm J Qual Patient Saf 2005; 31:372–378. 3. Poon EG, Keohane CA, Yoon CS, Ditmore M, Bane A, Levtzion-Korach O, et al. Effect of bar-code technology on the safety of medication administration. N Engl J Med. 2010; 362:1698–1707. 4. Mazer-Amirshahi M, Reid N, van den Anker J, Litovitz T. Effect of cough and cold medication restriction and label changes on pediatric ingestions reported to United States poison centers. J Pediatr. 2013; 163:1372–1376. 5. Doyon S, Tra Y, Klein-Schwartz W. Decrease in therapeutic errors involving prescription cough and cold medications in young children. J Pediatr Pharmacol Ther. 2012; 17:84–87. 6. Slone Epidemiology Center at Boston University. Patterns of medication use in the United States, 2006: a report from the Slone Survey. 2006 [July 15, 2013]; Available from: http://www.bu.edu/ slone/research/studies/slone-survey/. 7. Desai RJ, Williams CE, Greene SB, Pierson S, Caprio AJ, Hansen RA. Exploratory evaluation of medication classes most commonly involved in nursing home errors. J Am Med Dir Assoc 2013; 14:403–408. 8. Truitt CA, Brooks DE, Dommer P, LoVecchio F. Outcomes of unintentional beta-blocker or calcium channel blocker overdoses: a retrospective review of poison center data. J Med Toxicol 2012; 8:135–139. 9. Walsh KE, Dodd KS, Seetharaman K, Roblin DW, Herrinton LJ, Von Worley A, et al. Medication errors among adults and children with cancer in the outpatient setting. J Clin Oncol 2009; 27:891–896. 10. Shah K, Barker KA. Out-of-hospital medication errors: a 6-year analysis of the national poison data system. Pharmacoepidemiol Drug Saf 2009; 18:1080–1085. 11. Bronstein AC, Spyker DA, Cantilena LR Jr, Rumack BH, Dart RC. 2011 Annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 29th Annual Report. Clin Toxicol 2012; 50:911–1164. 12. AAPCC Generic Codes. In: POISINDEX® System [database on the Internet]. Truven Health Analytics, Inc. 2013 [cited May 28, 2014]. Available from: http://www.micromedexsolutions.com. 13. Drugs@FDA [database on the Internet]. U.S. Food and Drug Administration. [cited July 15, 2013]. Available from: http://www.fda.gov/ Drugs/InformationOnDrugs/UCM080163. 14. Intercensal Estimates of the Resident Population by Age and Sex for the United States: April 1, 2000 to July 1, 2010 [database on the Internet]. United States Census Bureau. 15. Annual Estimates of the Resident Population by Single Year of Age and Sex: April 1, 2010 to July 1, 2012 [database on the Internet]. United States Census Bureau. 16. Guyer B, Mavor A; Institute of Medicine Committee on Poison Prevention and Control. Forging a poison prevention and control system: report of an Institute of Medicine committee. Ambul Pediatr 2005; 5:197–200. 17. Miller TR, Lestina DC. Costs of poisoning in the United States and savings from poison control centers: a benefit-cost analysis. Ann Emerg Med. 1997; 29:239–245. 18. Spiller HA, Griffith JR. The value and evolving role of the U.S. Poison Control Center System. Public Health Rep. 2009; 124:359–363.
19. Qato DM, Alexander GC, Conti RM, Johnson M, Schumm P, Lindau ST. Use of prescription and over-the-counter medications and dietary supplements among older adults in the United States. JAMA. 2008; 300:2867–2878. 20. Fick DM, Maclean JR, Rodriguez NA, Short L, Heuvel RV, Waller JL, Rogers RL. A randomized study to decrease the use of potentially inappropriate medications among community-dwelling older adults in a southeastern managed care organization. Am J Manag Care 2004; 10:761–768. 21. Fillit HM, Futterman R, Orland BI, Chim T, Susnow L, Picariello GP, et al. Polypharmacy management in Medicare managed care: changes in prescribing by primary care physicians resulting from a program promoting medication reviews. Am J Manag Care 1999; 5:587–594. 22. Muir AJ, Sanders LL, Wilkinson WE, Schmader K. Reducing medication regimen complexity: a controlled trial. J Gen Intern Med 2001; 16:77–82. 23. Schmader KE, Hanlon JT, Pieper CF, Sloane R, Ruby CM, Twersky J, et al. Effects of geriatric evaluation and management on adverse drug reactions and suboptimal prescribing in the frail elderly. Am J Med 2004; 116:394–401. 24. Zarowitz BJ, Stebelsky LA, Muma BK, Romain TM, Peterson EL. Reduction of high-risk polypharmacy drug combinations in patients in a managed care setting. Pharmacotherapy. 2005; 25:1636–1645. 25. U. S. Food and Drug Administration. Using Over-the-Counter Cough and Cold Products in Children. 2008 [updated Oct 22]; Available from: http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm048515. htm. 26. Paulozzi LJ, Weisler RH, Patkar AA. A national epidemic of unintentional prescription opioid overdose deaths: how physicians can help control it. J Clin Psychiatry 2011; 72:589–592. 27. Centers for Disease C, Prevention. Vital signs: overdoses of prescription opioid pain relievers—United States, 1999–2008. MMWR Morbidity and mortality weekly report. 2011; 60:1487–1492. 28. Reifler LM, Droz D, Bailey JE, Schnoll SH, Fant R, Dart RC, Bucher Bartelson B. Do prescription monitoring programs impact state trends in opioid abuse/misuse? Pain Med 2012; 13:434–442. 29. Simeone R, Holland L. An Evaluation of Prescription Drug Monitoring Programs. Simeone Associates, Inc.; U.S. Dept of Justice, 2006. 30. Paulozzi LJ, Kilbourne EM, Desai HA. Prescription drug monitoring programs and death rates from drug overdose. Pain Med 2011; 12:747–754. 31. Baehren DF, Marco CA, Droz DE, Sinha S, Callan EM, Akpunonu P. A statewide prescription monitoring program affects emergency department prescribing behaviors. Ann Emerg Med 2010; 56:19–23 e1–3. 32. U.S. Food and Drug Administration. FDA Requires Additional Labeling for Over-the-Counter Pain Relievers and Fever Reducers to Help Consumers Use Products Safely 2009. Available from: http:// www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2009/ ucm149573.htm (accessed 15 July 2014). 33. Manthripragada AD, Zhou EH, Budnitz DS, Lovegrove MC, Willy ME. Characterization of acetaminophen overdose-related emergency department visits and hospitalizations in the United States. Pharmacoepidemiol Drug Saf 2011; 20:819–826. 34. LaPointe NM, Jollis JG. Medication errors in hospitalized cardiovascular patients. Arch Intern Med 2003; 163:1461–1466. 35. Field TS, Mazor KM, Briesacher B, Debellis KR, Gurwitz JH. Adverse drug events resulting from patient errors in older adults. J Am Geriatr Soc 2007; 55:271–276. 36. Hayes BD, Klein-Schwartz W, Gonzales LF. Causes of therapeutic errors in older adults: evaluation of National Poison Center data. J Am Geriatr Soc 2009; 57:653–658. 37. Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999–2008. JAMA 2010; 303: 235–241. 38. Preventing Medication Errors. Washington, DC: Institute of Medicine, Committee on Identifying and Preventing Medication Errors; 2007.
Clinical Toxicology vol. 52 no. 8 2014
POISON CENTRE
Medication errors reported to U.S. Poison Control Centers, 2000–2012 T. J. BROPHY,1,2 H. A. SPILLER,1,3 M. J. CASAVANT,1,3 T. CHOUNTHIRATH,2 M. D. SMITH,2 and H. XIANG1,2 1The
Ohio State University College of Medicine, Columbus, OH, USA for Injury Research and Policy at the Research Institute of Nationwide Children’s Hospital, Columbus, OH, USA 3Central Ohio Poison Center, Columbus, OH, USA Clinical Toxicology Downloaded from informahealthcare.com by University of Otago on 09/11/14 For personal use only.
2Center
Context. Previous studies of medication errors have largely focused on healthcare facilities and have not reported generalizable national trends among out-of-hospital medication errors. Objective. We sought to understand U.S. trends in medication errors, including the agerelated risks, the involved medications, and the medical outcomes. Materials and methods. We performed a retrospective analysis of National Poison Data System (NPDS) data from the American Association of Poison Control Centers for years 2000–2012. Medication error cases were analyzed by age, gender, pharmaceutical involved, substance rank, dosing error type, management site, level of healthcare received, and medical outcome. Trends in medication error rates were analyzed using Poisson regression. Results. From 2000 to 2012, the NPDS recorded 2,913,924 calls reporting unintentional pharmaceutical-related errors that met inclusion criteria. Non-healthcare facility calls comprised 99.2% calls related to unintentional therapeutic errors. Eighty-seven percent of medication errors were managed on site. The annual medication error rate for all callers per 10,000 U.S. population increased significantly (p ⬍ 0.0001) by 69.8% from 2000 (4.98 calls per 10,000 population) to 2012 (8.46 calls per 10,000 population). Among adults aged 20 years and older, age was positively correlating (r ⫽ 0.96) with the rate of medication error. Analgesics were the most frequent pharmaceutical class involved in medication errors for ages 6–49 (N ⫽ 221,061). Among ages 20–49 years, opioid-related medication errors decreased by 7.9% from 2010 to 2012. Cardiovascular drugs were the leading source of injury among all ages (N ⫽ 14,440) and also the leading pharmaceutical class involved in medication errors among adults 50 years and older (N ⫽ 187,760). Conclusion. Medication errors continue to be a source of preventable injury with increasing incidence across the out-of-hospital population. Keywords Poison Control Centers; Unintentional therapeutic errors; Analgesics; Cardiovascular drugs
per week.6 Previous research regarding out-of-hospital medication errors was limited to state-wide studies, at-risk populations, or specific medications, limiting the generalizability of results to the entire population.7–9 In 2006, a 6-year retrospective analysis utilizing national poison control center data described out-of-hospital medication errors, indicating high frequencies of errors involving analgesics, cardiovascular agents, and cold and cough medications.10 However, this 2006 study was limited to simple counts of error scenario characteristics and did not provide information regarding temporal patterns or age associations.
Introduction Background Medication errors are a significant source of preventable mortality and healthcare costs, as detailed in the Institute of Medicine’s seminal report.1 A 2005 study estimated that adverse drug events leading to outpatient treatment increased from 2.9 million to 4.3 million from 1995 to 2001.2 In healthcare facilities, electronic medication dispensing systems have proven to be an effective intervention to reduce medication errors.3 In the outpatient setting, interventions for the pediatric population have dramatically decreased cold and cough medication errors.4,5
Goals of this investigation We analyzed call data from the National Poison Data System (NPDS) of the American Association of Poison Control Centers (AAPCC). Due to its standardized data collection, large sample size, and near real-time data, the NPDS is well-suited for medication error surveillance. The goal of our study is to characterize the trends of medication errors, including the age-related risks and the medications involved.
Importance Studies of medication errors for all ages are warranted, given that 82% of U.S. adults take at least one medication Received 12 March 2014; accepted 4 August 2014. Address correspondence to Huiyun Xiang, MD, MPH, PhD, Center for Injury Research and Policy, The Research Institute at Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, USA. Tel: ⫹ 614-355-5850. E-mail: [email protected]
880
Medication errors 881
Methods
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Study design and setting This study was a 13-year retrospective analysis of data from the NPDS. The NPDS is a proprietary database maintained by the AAPCC. The NPDS collects data in near real-time for every call to the nation’s regional poison centers, which serve the entire population of the U.S. and its territories.11 This study was reviewed by the IRB of the authors’ institution and judged to be exempt. Selection of participants NPDS data were requested for all “unintentional therapeutic error” calls from January 1, 2000 to December 31, 2012 involving pharmaceutical substances as determined by the AAPCC generic substance coding system, which is maintained by Micromedex POISINDEX ® Managements.11,12 In NPDS, an unintentional therapeutic error is defined as “an unintentional deviation from a proper therapeutic regimen that results in the wrong dose, incorrect route of administration, administration to the wrong person, or administration of the wrong substance”. Drug interactions resulting from unintentional administration of drugs or foods which are known to interact are also included.11 Only exposures to medications or products used as medications are included in our study. Specifically excluded were pediatric exploratory ingestions, intentional drug misuse and drug abuse, and suicidal or malicious drug exposures. Additionally, calls were limited geographically to the 50 United States and District of Columbia so that trend analysis could be conducted using available U.S. population data. In this report, the terms “unintentional therapeutic error” and “medication error” are used interchangeably. The AAPCC records separate exposure data for each pharmaceutical reported in calls involving multiple substances, resulting in the number of medication error exposures exceeding the total number of calls. Because the majority of poison center calls are self-reported, without healthcare personnel involvement, the term “call” or “caller” refers to an individual experiencing a medication error. In this report, the term “exposure” refers to each separate pharmaceutical reported for a given caller. For calls with multiple pharmaceuticals reported, data analyses were limited to only the pharmaceutical with the greatest contribution to any clinical effects as determined by the poison center specialist managing the call, denoted by substance rank. Unless noted otherwise, our analysis focused on individual callers and the principal pharmaceutical determined by the poison center specialist. Methods and measurements Data were analyzed by subject’s age, gender, involved pharmaceuticals, substance rank, dosing error type, management site, level of healthcare received, and medical outcome. Pharmaceuticals were classified according to the NPDS generic coding system and by consulting a FDA drug database.13 Under AAPCC pharmaceutical coding, the analgesic Copyright © Informa Healthcare USA, Inc. 2014
category encompasses prescription medications, including opioids, and non-prescription analgesics, such as non-steroidal anti-inflammatory drugs (NSAIDs). In this study, opioid pharmaceuticals include opioids and any opioid combination pharmaceuticals; acetaminophen (paracetamol) drugs include acetaminophen and any non-opioid acetaminophen combination pharmaceuticals; and NSAIDs include NSAIDs and any non-opioid, non-acetaminophen combination NSAIDs. Cold and cough preparations include combination pharmaceutical products, such as antihistamine and/or decongestant products with analgesics. Hormone-based pharmaceuticals include medications such as insulin, oral hypoglycemics, thyroid preparations, and steroids. Medical outcomes and dosing error scenarios were classified by poison center specialists according to standard NPDS definitions.11 In this study, injury was defined as any medication error causing a medical outcome coded as moderate effect, major effect, or death. Similar to the NPDS Annual Report, children were defined as less than 20 years of age, with age subgroups of 0–5 years, 6–12 years, and 13–19 years. Adults were defined as aged 20 years and older, with age subgroups by decade of life and the most senior age group as 80 years and older.11 Analysis NPDS data were analyzed using SAS 9.3 (SAS Institute, Inc., Cary, NC). Most data analysis was descriptive in nature and limited to event frequencies for the variables under study. U.S. Census Bureau July 1 intercensal and postcensal resident population estimates for 2000 through 2012 were used as the denominator for the overall and age-specific medication error rate calculations.14,15 Analysis was performed by the stated age groups, with results displaying combined age groups when similar trends were observed. Pearson correlation analysis was used to evaluate the correlations between age and the medication error rate, the percentage of injuries, and the percentage of multiple-substance errors. The Pearson product-moment correlation coefficient was represented by r. To investigate the overall and age group-specific trends in the annual rate of medication error calls, Poisson models were fit to the data with year as the independent variable. We used the Pearson method to estimate a scale parameter when there was evidence of overdispersion (greater variability than expected with the given model). Significant trends in the annual rate of calls are reported as the percentage changed with a p-value from the Poisson regression. All statistical significance was established at the two-tailed significance level of α ⫽ 0.05.
Results Study population From 2000 through 2012, the NPDS recorded 2,980,042 calls reporting pharmaceutical-related unintentional therapeutic errors, of which 2,913,924 calls (97.8%) met the inclusion criteria (Table 1). Calls were excluded if: (1) the events were confirmed non-exposures (4,479 cases), (2) the pharmaceuticals were unrelated to the clinical effects (53,748
882 T. J. Brophy et al. Table 1. Total number of medication errors by pharmaceutical class for all ages, years 2000–2012. Single-substance medication error calls
Injuries†
Calls
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Pharmaceutical class Analgesics Cold and cough preparations Cardiovascular drugs Antihistamines Antimicrobials Hormones and hormone antagonists Antidepressants Sedatives, Hypnotics, Antipsychotics Gastrointestinal preparations Anticonvulsants Stimulants Asthma therapies Vitamins Anticholinergic drugs Eye, Ear, Nose, and Throat Preparations Miscellaneous drugs Topical preparations Electrolytes and minerals Muscle relaxants Diuretics Anticoagulants Dietary Supplements, Herbals, Homeopathics Anesthetics Veterinary drugs Unknown drug Serums, Toxoids, Vaccines Antineoplastics Diagnostic agents Narcotic antagonists Radiopharmaceuticals Total
All medication error calls*
Injuries†
Calls
Change in no. of calls, 2000–2012‡
N
%
N
%
N
%
N
%
%
469322 316807 226882 221654 220274 151321 118791 110924 83864 74325 72029 62999 56611 54221 51512 49598 37076 23712 22336 18536 17955 16783 9342 9087 8189 7182 6509 1980 382 34 2520237
18.6 12.6 9.0 8.8 8.7 6.0 4.7 4.4 3.3 3.0 2.9 2.5 2.3 2.2 2.0 2.0 1.5 0.9 0.9 0.7 0.7 0.7 0.4 0.4 0.3 0.3 0.3 0.1 0.0 0.0
6450 2855 9430 1440 1659 6157 4641 5318 1297 3596 2504 1506 237 284 1446 1624 650 383 1118 389 563 404 559 81 269 68 265 142 61 5 55401
11.6 5.2 17.0 2.6 3.0 11.1 8.4 9.6 2.3 6.5 4.5 2.7 0.4 0.5 2.6 2.9 1.2 0.7 2.0 0.7 1.0 0.7 1.0 0.1 0.5 0.1 0.5 0.3 0.1 0.0
534874 369711 306091 249079 229547 171094 145918 138338 90377 100734 83731 67812 59818 55564 52627 60395 37475 25636 26415 23003 22446 18011 9688 9368 8734 7861 7052 2014 471 40 2913924
18.4 12.7 10.5 8.6 7.9 5.9 5.0 4.8 3.1 3.5 2.9 2.3 2.1 1.9 1.8 2.1 1.3 0.9 0.9 0.8 0.8 0.6 0.3 0.3 0.3 0.3 0.2 0.1 0.0 0.0
8410 3481 14440 1705 1827 7558 5907 6871 1491 4634 2911 1623 269 366 1472 2119 671 426 1421 511 681 455 609 87 299 79 282 146 78 5 70834
11.9 4.9 20.4 2.4 2.6 10.7 8.3 9.7 2.1 6.5 4.1 2.3 0.4 0.5 2.1 3.0 0.9 0.6 2.0 0.7 1.0 0.6 0.9 0.1 0.4 0.1 0.4 0.2 0.1 0.0
91.9 ⫺ 31.2 126.4 133.6 79.3 192.0 76.8 129.6 97.6 105.8 139.7 19.7 95.2 3206.7 66.9 217.3 98.6 95.7 98.7 91.2 316.8 338.4 49.9 66.5 149.1 136.6 239.2 34.2 338.5 200.0
*All Medication Error Calls includes single-substance and multiple-substance exposure calls. Multiple-substance calls are categorized according to the primary pharmaceutical responsible for clinical effects, as determined by the poison control specialist. †Injuries include all medical outcomes coded as moderate effect, major effect, or death. ‡Percent change in the number of calls from 2000 to 2012 is calculated as the overall percent change in the number of calls received for each pharmaceutical class.
cases), or (3) the case occurred outside the 50 United States or District of Columbia (7,891 cases). All single-substance (86.5%) and multiple-substance calls (13.5%) were included in this study. Non-healthcare facility calls comprised 99.2% of study calls. Overview Children under 20 years of age were involved in 47.3% of all medication errors reported, with children younger than 6 years involved in 27.4% of all medication errors. More than half (55.8%) of medication errors among children involved males. More than two-thirds 67.9% of all adult (ⱖ 20 years of age) medication errors involved females. The most common dosing error within each age group was inadvertently taking medication twice, attributed to 31.8% of all calls. Among the 70,834 medication error injuries, moderate clinical effect (N ⫽ 65,825) was much more common than major clinical effect (N ⫽ 4,495) or death (N ⫽ 514). Eighty-seven percent
of all medication error calls were able to be managed on site, not at a healthcare facility. Among the 240,851 (8.3%) callers that received healthcare facility treatment, most were treated and released (77.4%), with the remaining patients being admitted to non-critical care units (12.2%), critical care units (9.6%), or psychiatric units (0.7%). The rate of healthcare facility use per 100,000 population increased significantly (p ⬍ 0.0001) by 104.1% from 3.86 calls in 2000 to 7.87 calls in 2012. Medication errors by age group The annual medication error rate for all callers per 10,000 U.S. population increased significantly (p ⬍ 0.0001) by 69.8% from 4.98 calls in 2000 to 8.46 calls in 2012. A linear trend was observed across all age groups, except children 0–5 years old, in which the direction of the trend changed. Among children, the rate of medication errors decreased as age increased (r ⫽ ⫺ 0.97). Children under 6 years old Clinical Toxicology vol. 52 no. 8 2014
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Medication errors 883 (25.76 calls per 10,000 population) had over twice the rate of medication errors as children ages 6–12 years (10.45 calls per 10,000) and five times the rate for ages 13–19 years (4.85 calls per 10,000 population). The annual medication error rates among children under 6 years increased significantly by 45.7% (p ⬍ 0.0001) from 2000 to 2005 followed by a significant decrease of 11.5% (p ⬍ 0.0001) from 2005 to 2010.. The annual medication error rates increased significantly by 72.0% (p ⬍ 0.0001) for children 6–12 years old and 67.3% (p ⬍ 0.0001) for teenagers 13–19 years old. The annual medication error rates peaked in 2009 for both 6- to 12-year olds (12.64 calls per 10,000 population) and 13- to 19-year olds (5.72 calls per 10,000 population). Among adults, age of the population was positively correlated (r ⫽ 0.96) with the rate of a medication error, with significant (p ⬍ 0.0001) linear increases in annual medication error rates observed in all age groups from 2000 to 2012 (Fig. 1). All adult age groups reached a peak medication error rate in 2011, with maximum rates ranging from 4.00 (ages 20–29 years) to 12.86 (ages ⱖ 80 years) calls per 10,000 population. Age of the population was also positively correlated (r ⫽ 0.90) with the percentage of injuries and positively correlated (r ⫽ 0.92) with the percentage of multiple-substance errors, ranging from 15.2% in 20- to 29-year olds to 23.9% in adults 80 years and older. Medication errors by pharmaceutical class Among all medication errors, the most frequently involved pharmaceutical classes were analgesics, cold and cough preparations, and cardiovascular drugs (Table 1). During the study period, the annual number of cardiovascular and analgesic medication errors increased by 126.4% and 91.9%, respectively. Cold and cough preparations were the only class observed to decrease (⫺ 31.2%) in the annual number of errors. Anticholinergic drugs had the greatest percent increase (3206.7%) in the number of error calls from 2000 (240 calls) to 2012 (7,936 calls). Among all medication error injuries, 20.4% involved cardiovascular drugs, 11.9%
involved analgesics, and 10.7% involved hormone-based pharmaceuticals. Analgesic medication errors were among the top three most frequently reported pharmaceutical classes for every age group (Table 2). Among children under 6 years old, the majority of medication errors were once due to cold and cough preparations; however, cold and cough preparation errors showed a dramatic decrease after 2006 and analgesics became the leading medication involved in errors from 2008 to 2012 (Fig. 2). Analgesics were the leading pharmaceutical class involved in medication errors within each age group from 6 to 49 years old, accounting for 18.8% of calls (N ⫽ 221,061) in this age range. Among adults over 50 years, analgesics were the second most reported medication class (N ⫽ 90,841, 11.8%). Across all ages, opioids accounted for 54.9% (N ⫽ 4,616) of all injuries due to analgesics, with fewer injuries being reported for acetaminophen-based drugs (N ⫽ 2,225) or NSAIDs (N ⫽ 1,506). Of all opioid medication error calls, 3.7% resulted in an injury, as compared to injuries documented in 1.1% of acetaminophen-based error calls and 0.7% of NSAID error calls. A subanalysis was performed to characterize the agerelated trends by analgesic subclass. Due to similarities in trends among age groups, the results are presented by ages under 20 years old (children), ages 20–49 years old, and ages 50 and older. Among children, acetaminophen-based drugs accounted for 46.4% of medication errors (N ⫽ 138,361), followed by NSAIDs (N ⫽ 130,232, 43.7%) and opioids (N ⫽ 29,293, 9.8%; Fig. 3). For adults aged 20–49 years, opioids were the leading class of analgesics involved in medication errors (N ⫽ 43,869, 36.7%), followed by NSAIDs (N ⫽ 42,667, 35.7%) and acetaminophen-based drugs (N ⫽ 32,371, 27.1%; Fig. 4). Although opioids increased 88.1% in annual medication error frequency from 2000 to 2012, opioid medication errors decreased 7.9% from 2010 to 2012. Hydrocodone/acetaminophen was the leading opioid involved in medication errors for ages 20–49 years old, accounting for 30.4% (N ⫽ 13,337) of opioid medication errors and paralleling the overall opioid decline by decreasing
Fig. 1. Rate of medication error calls per year for adults, ages ⱖ 20 years. Copyright © Informa Healthcare USA, Inc. 2014
Antimicrobials (5.6%) Antidepressants (5.7%) Sedatives, Hypnotics, Antipsychotics (8.1%)
Anticholinergic Drugs (7.5%) Antimicrobials (5.7%) Hormone-based Pharmaceuticals (8.2%)
Antimicrobials (6.2%)
Sedatives, Hypnotics, Antipsychotics (6.4%)
Antimicrobials (7.8%) Antihistamines (8.0%)
Asthma Therapies (4.5%) 5
Gastrointestinal Preparations (4.0%)
Antimicrobials (6.6%)
Cold and Cough Preparations (11.3%) Cardiovascular Drugs (9.2%) Stimulants (8.6%) Antihistamines (10.6%) 4
Cold and Cough Preparations (12.2%)
Antidepressants (9.1%) Stimulants (11.9%) Antihistamines (12.4%) Antimicrobials (11.3%) 3
Antimicrobials (12.3%)
Analgesics (15.2%) Analgesics (18.3%) Analgesics (21.2%) 2
Antihistamines (18.2%)
Stimulants (10.2%)
Cold and Cough Preparations (9.5%) Antidepressants (8.6%)
Antihistamines (7.6%)
Cold and Cough Preparations (9.0%) Sedatives, Hypnotics, Antipsychotics (7.3%)
Analgesics (11.0%) Hormone-based Pharmaceuticals (9.3%) Antidepressants (8.8%) Cardiovascular Drugs (10.6%)
Sedatives, Hypnotics, Antipsychotics (7.7%) Cold and Cough Preparations (7.7%)
Hormone-based Pharmaceuticals (12.1%) Analgesics (12.7%) Cardiovascular Drugs (11.0%) Antidepressants (11.3%)
Cold and Cough Preparations (14.2%) Antidepressants (9.5%) Antihistamines (11.3%)
Antidepressants (9.4%)
Cardiovascular Drugs (22.9%) Cardiovascular Drugs (27.5%) Analgesics (17.8%) Analgesics (18.7%) Analgesics (23.4%) Analgesics (23.1%) Antihistamines (16.1%) Cold and Cough Preparations (20.9%) Analgesics (32.2%) Cold and Cough Preparations (34.7%) 1
2000 2012 2000 2012 2000
Cold and Cough Preparations (20.8%) Analgesics (20.6%)
Analgesics (18.1%)
2000 2012 2000 2012
Age 20–29 Age 13–19 Age 6–12 Age 0–5 Pharmaceutical class rank
Table 2. Most frequently reported pharmaceutical classes in medication errors as a percent of age group total errors in 2000 and 2012.
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Age 30–49
2012
2000
Age ⬎ 50
2012
884 T. J. Brophy et al. 9.7% from 2010 (N ⫽ 1,310) to 2012 (N ⫽ 1,183). After 2009, there was also decreasing number of calls related to acetaminophen medication errors among adults, 20–49 years of age. Among adults aged 50 years and over, opioids represented 44.5% (N ⫽ 40,419) of analgesic errors, with lower percentages of NSAID (N ⫽ 30,619, 33.7%) and acetaminophenbased (N ⫽ 19,229, 21.2%) medication errors (Fig. 5). Cardiovascular medications were the most frequently reported medication error among adults aged 50 years or older (N ⫽ 187,760, 24.3%). However, cardiovascular medication errors were also the second most frequently reported medication class among ages 30–49 years (N ⫽ 44,078), with an increasing trend from 2000 (N ⫽ 2,350) to 2012 (N ⫽ 4,128; Table 2). A subanalysis of cardiovascular medication errors in adults aged 50 years or older was performed to describe the contributing agents (Fig. 6). The annual frequency of cardiovascular medication errors in adults aged 50 years and older increased 133.8% from 2000 (N ⫽ 8,138) to 2012 (N ⫽ 19,027). Beta blockers were the leading cardiovascular drug subclass involved in medication error calls (N ⫽ 50,670, 27.0%), followed by calcium antagonists (N ⫽ 36,480, 19.4%), angiotensin-converting enzyme (ACE) inhibitors (N ⫽ 25,739, 13.7%), antihyperlipidemics (N ⫽ 20,212, 10.8%), and angiotensin receptor blockers (N ⫽ 17,884, 9.5%). Among the 9,598 injuries related to cardiovascular medications among adults aged 50 years or older, beta blockers accounted for 29.1% of these injuries and calcium antagonists accounted for 28.0%.
Discussion This study provided an overview of trends in medication errors over a 13-year period in the U.S. Among all age groups except children under 6 years, the annual rate of medication errors has increased significantly from 2000 to 2012. The number of medication errors reported to poison control centers highlights the extent of the problem, affecting all ages and nearly all pharmaceuticals. The vast majority of medication errors do not result in injury, and very few of these injuries result in major clinical effects or deaths, which emphasizes that healthcare treatment is often not necessary. During the study period, over 2.5 million individuals (87.2% of callers) that experienced a medication error were able to be managed on site, typically at home, without further medical treatment. Although this study did not evaluate what proportion of these callers would have sought medical treatment otherwise, the poison control center system has been estimated previously to save between $310 million to $900 million annually from decreased utilization of other healthcare providers.16–18 The aging of the U.S. population is an important factor that will likely only exacerbate current trends in medication errors. Increasing age has been associated previously with increasing rates of medication use and polypharmacy.6,19 Our results show that among adults 20 years or older, as age increased so did the rate of medication errors, the percentage of multiple-substance errors, and the proportion injured. Clinical Toxicology vol. 52 no. 8 2014
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Fig. 2. Number of medication error calls by pharmaceutical class, ages ⬍ 6 years.
Although there have been studies regarding successful interventions to reduce polypharmacy among older adults,20–24 our findings suggest that medication errors continue to occur at increasing rates in this population. There was a significant decrease in the annual rate of unintentional medication errors among children under 6 years old from 2005 to 2012. This decrease was mainly driven by the decrease in the annual number of cold and cough medication errors (Fig. 2), which coincided with the concerted efforts to restrict cold and cough medicine use in this age group by the Food and Drug Administration (FDA) and the voluntary removal of products marketed for very young children as well as voluntary label changes by the Consumer Healthcare Products Association (CHPA).4,5,25 Despite the dramatic decline seen in cold and cough medication errors, analgesic and antihistamine medication errors continued to increase (Fig. 2). It is possible that the decrease in availability of cold and cough preparations in the home for this age group has led to the increased use of analgesics and antihistamines, but further study is needed. Analgesics were the leading class of medication errors in each age group from 6 to 49 years old, with the annual
frequency of analgesic medication errors increasing in all age groups from 2000 to 2012. In adults aged 20–49 years, opioid medications were the most frequently reported analgesic medication errors, increasing 88.1% from 2000 to 2012. The increase in opioid medication errors is not unexpected, as the documented increase in the per capita sales of opioid medications has been correlated to increases in unintentional overdoses and deaths.26,27 However, after steadily increasing from 2000 to 2010, the number of opioid medication errors in ages 20–49 decreased by nearly 8% from 2010 to 2012, despite the annual call rate remaining relatively constant among these age groups during this time (Fig. 1). It is possible that this change in opioid trend may be linked to the considerable efforts at both the state and federal levels to implement the prescription drug monitoring programs (PDMPs) and related legislation. Previous studies have shown the potential impact of PDMPs on the mitigation of opioid abuse and misuse.28 However, there have been mixed findings as to whether PDMPs have been linked to decreased opioid use.29,30 Alternatively, it is possible that PDMPs might have impacted physician behavior, leading to more judicious opioid prescribing practices.31 Lastly, the focus on rising
Fig. 3. Number of analgesic medication error calls by subclass, ages ⬍ 20 years. Copyright © Informa Healthcare USA, Inc. 2014
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886 T. J. Brophy et al.
Fig. 4. Number of analgesic medication error calls by subclass, ages 20–49 years.
opioid overdose trends by news media outlets and governmental agencies might have elevated social awareness of opioid use, leading to decreased frequencies of medication errors. As more states fully implement PDMPs, future studies should address their efficacy to reduce not only abuse and intentional misuse, but also unintentional errors. Acetaminophen (non-opioid) calls among 20- to 49-year olds also showed declines after 2009, perhaps related to FDA required label changes in 2009 for over the counter pain relievers and fever reducers.32 Further consideration of this trend and trends in acetaminophen overdose-related emergency department visits and hospitalizations are merited.33 Cardiovascular drugs were a major source of medication errors throughout the study, responsible for the most medication errors in adults 50 years and older and the third most errors for all ages. Of great importance is the observation that although cardiovascular drugs accounted for 10.5% of calls in this study, they were responsible for 20.4% of all injuries due to medication errors. Previous studies have highlighted the impact of cardiovascular drugs in specific populations, such as adults aged 65 years and older or patients at hospitals and nursing homes.34–36
However, our study also found a significant increase in cardiovascular medication errors in adults 30–49 years old. The subanalysis of cardiovascular agents showed the relative number of medication errors by specific subclasses. Although reportedly used less frequently than antihyperlipidemics, beta blockers and calcium channel antagonists showed higher frequencies of medication errors.6 Because beta blockers and calcium channel antagonists can be used as both antihypertensive agents and antiarrhythmic agents, patient confusion about their function may increase their involvement in medication errors. Furthermore, the potential serious side effects of their inappropriate use may cause them to be recognized and reported more frequently in comparison to other medications. Due to the association of obesity with cardiovascular disease, as the prevalence of obesity remains high and continues to affect younger patients,37 treatment with cardiovascular drugs will likely increase. Therefore, future studies regarding medication errors involving cardiovascular agents must correspondingly expand their study population to include middle-aged adults so that the complete study population is considered and appropriate interventions can be designed.
Fig. 5. Number of analgesic medication error calls by subclass, ages ⱖ 50 years. Clinical Toxicology vol. 52 no. 8 2014
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Medication errors 887
Fig. 6. Number of cardiovascular medication error calls by subclass, ages ⱖ 50 years.
Although interventions to reduce medication errors in the hospital setting have been studied and shown effective in recent years, less information is available on ambulatory interventions to prevent medication errors. Medication selfcare educational programs and medication reconciliation have previously been proposed as strategies to reduce outof-hospital medication errors; however, other strategies to prevent errors in the ambulatory population have not been well-studied.38 Further research should address the causes of medication errors so that specific interventions can be designed. There are a number of limitations in this study, including the inherent limitations of retrospective studies and the voluntary nature of reporting medication errors. Another limitation is that our study likely underestimated the true prevalence of medication errors, as many individuals might have made errors without recognition or sought information from online resources. Injury may also be underestimated, as 2.2% of medical outcomes were potentially toxic but unable to be followed. Additionally, because we do not know the daily number of medications taken by each patient, we cannot take this into account as a confounding factor in the correlation analysis between caller age, multiple-substance errors, and injury. Nevertheless, observation of these trends helps to further illustrate the scope of the problem and identify areas of future research. Finally, there was also the potential for error in multiple-substance calls when assigning the drug most responsible for clinical effects. However, as 86.5% of calls were single-substance reports and as there have been no reported systemic biases in the NPDS recording system, the error of assigning the most responsible drug was likely very small.
Conclusions The NPDS provides a large, accessible database conducive to characterizing medication error trends in the out-of-hospital population. From 2000 to 2012, the medication error rate increased significantly among all age groups except for Copyright © Informa Healthcare USA, Inc. 2014
children under 6 years. Among adults aged 20 years or older, the error rate increased with increasing age. Furthermore, analgesics accounted for the greatest number of medication errors in young and middle-aged adults, but adults 50 years and older most frequently reported cardiovascular medication errors. Cardiovascular drugs were the leading source of injury for all age groups.
Disclaimer The American Association of Poison Control Centers (AAPCC; http://www.aapcc.org/) maintains the national database of information logged by the country’s regional poison centers (PCs). 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 (e.g., an ingestion, inhalation, or 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 PCs and data referenced from the AAPCC should not be construed to represent the complete incidence of national exposures to any substance(s).
Acknowledgements Krista Kurz Wheeler is acknowledged for her assistance in revising and editing this manuscript.
Declaration of interest This study was funded in part by the Barnes Medical Student Research Scholarship of The Ohio State University College of Medicine. Efforts of Thiphalak Chounthirath and Dr. Huiyun Xiang were funded by a research grant from the National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, US Department of
888 T. J. Brophy et al. Health and Human Services (Grant #:1R49 CE002106; PI: Dr. Huiyun Xiang). The views expressed here are those of the authors and do not necessarily reflect the official views of the Centers for Disease Control and Prevention.
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