Emergency Department Visits for Overdoses of Acetaminophen-Containing Products

      Background

      Limited national data on the circumstances of acetaminophen overdoses have hindered identification and implementation of prevention strategies.

      Purpose

      To estimate the frequency of and characterize risks for emergency department visits for acetaminophen overdoses that were not related to abuse in the U.S.

      Methods

      Data were collected from two components of the National Electronic Injury Surveillance System from January 1, 2006, through December 31, 2007, and analyzed from 2009 to 2010 to estimate the annual number of emergency department visits for non-abuse-related acetaminophen overdose by patient demographics, treatments, and type and amount of acetaminophen-containing product ingested.

      Results

      There were an estimated 78,414 emergency department visits (95% CI=63655, 93172) annually for non-abuse-related overdoses of acetaminophen-containing products. Most emergency department visits for acetaminophen overdose were for self-directed violence (69.8%, 95% CI=66.4%, 73.2%), with the highest rate among patients aged 15–24 years (46.4 per 100,000 individuals per year). Unsupervised ingestions by children aged <6 years accounted for 13.4% (95% CI=11.0%, 15.9%) of visits for acetaminophen overdoses (42.5 per 100,000 individuals per year). Therapeutic misadventures accounted for 16.7% (95% CI=14.0%, 19.5%) of visits and most involved overuse for medicinal effects (56.1%, 95% CI=50.6%, 61.6%) rather than use of multiple acetaminophen-containing products or dose confusion.

      Conclusions

      Non-abuse-related overdoses of acetaminophen products lead to many emergency department visits each year, particularly emergency department visits for self-directed violence. Acetaminophen overdose prevention efforts will likely need to be multidimensional.

      Introduction

      Acetaminophen has been used to treat pain and fever for more than 50 years. It is sold over the counter (OTC) as a single-ingredient product or in combination with other ingredients to treat symptoms of allergies, colds and upper respiratory tract infections, migraines, sleep disorders, and other conditions. To treat more severe pain, acetaminophen is combined with opioid analgesics in numerous prescription products. A 1-week prevalence survey found that acetaminophen, taken either as a single ingredient or in a combination product, was the most commonly used drug among adults in the U.S.
      • Kaufman D.W.
      • Kelly J.P.
      • Rosenberg L.
      • Anderson T.E.
      • Mitchell A.A.
      Recent patterns of medication use in the ambulatory adult population of the U.S.: the Slone Survey.
      Combination acetaminophen/hydrocodone products have been the most frequently dispensed prescription drugs in the U.S. since 1997.
      U.S. Food and Drug Administration
      Recommendations for FDA interventions to decrease the occurrence of acetaminophen hepatotoxicity.
      Acetaminophen is considered to be safe and effective when used as directed; however, because of its relatively narrow therapeutic index, exceeding the maximum recommended dose can lead to liver toxicity. For adults, a single dose of 10–15 g can cause hepatic necrosis, and for some the toxicity threshold may be lower.
      • Larson A.M.
      Acetaminophen hepatotoxicity.
      • Amar P.J.
      • Schiff E.R.
      Acetaminophen safety and hepatotoxicity—where do we go from here?.
      Manifestations of toxicity range from abnormal liver function tests to acute liver failure (ALF) and death,
      • Hendrickson R.G.
      • Bizovi K.E.
      Acetaminophen.
      and the U.S. Food and Drug Administration (FDA) convened an advisory committee meeting in June 2009 to review data on liver injury related to use of acetaminophen and to suggest potential harm-reduction strategies.
      U.S. Food and Drug Administration
      June 29–30, 2009: Joint meeting of the Drug Safety and Risk Management Advisory Committee with the Anesthetic and Life Support Drugs Advisory Committee and the Nonprescription Drugs Advisory Committee: meeting announcement.
      Previous assessments of acetaminophen-related overdoses and liver injury in the U.S. have been based on data from single institutions,
      • Gyamlani G.G.
      • Parikh C.R.
      Acetaminophen toxicity: suicidal vs accidental.
      tertiary care centers,
      • Larson A.M.
      • Polson J.
      • Fontana R.J.
      • et al.
      Acute Liver Failure Study Group
      Acetaminophen-induced acute liver failure: results of a U.S. multicenter, prospective study.
      • Squires Jr, R.H.
      • Shneider B.L.
      • Bucuvalas J.
      • et al.
      Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group.
      or surveillance systems that are no longer operational.
      • Bower W.A.
      • Johns M.
      • Margolis H.S.
      • Williams I.T.
      • Bell B.P.
      Population-based surveillance for acute liver failure.
      Data on the context of and risk factors for acetaminophen overdoses and the specific type of acetaminophen-containing products involved are limited.
      • Nourjah P.
      • Ahmad S.R.
      • Karwoski C.
      • Willy M.
      Estimates of acetaminophen (paracetamol)–associated overdoses in the U.S..
      Therefore, nationally representative public health surveillance data were analyzed to characterize emergency department visits for non-abuse-related acetaminophen overdoses in the U.S.

      Methods

      Data Source

      National estimates of the number of emergency department visits for overdoses involving acetaminophen-containing products were based on data from two components of the National Electronic Injury Surveillance System (NEISS)—the Cooperative Adverse Drug Event Surveillance project (NEISS–CADES) and a special study of the All Injury Program (NEISS–AIP) on self-directed violence.
      Both NEISS–CADES and NEISS–AIP use the same national stratified probability sample of 63 hospitals with a minimum of six beds and a 24-hour emergency department in the U.S. and its territories and have been described in detail elsewhere.
      U.S. Consumer Product Safety Commission
      National Electronic Injury Surveillance System—all injury program sample design and implementation.
      • Budnitz D.S.
      • Pollock D.A.
      • Weidenbach K.N.
      • Mendelsohn A.B.
      • Schroeder T.J.
      • Annest J.L.
      National surveillance of emergency department visits for outpatient adverse drug events.
      • Jhung M.A.
      • Budnitz D.S.
      • Mendelsohn A.B.
      • Weidenbach K.N.
      • Nelson T.D.
      • Pollock D.A.
      Evaluation and overview of the National Electronic Injury Surveillance System—Cooperative Adverse Drug Event Surveillance Project (NEISS–CADES).
      CDC
      Nonfatal self-inflicted injuries among adults aged ≥65 years—U.S., 2005.
      • Schroeder T.J.
      • Ault K.
      National Electronic Injury Surveillance System (NEISS) sample design and implementation from 1997 to present.
      For NEISS–CADES, trained coders at each participating emergency department review clinical records of every visit and report data to identify adverse drug events (ADEs) based on the verbatim clinical diagnoses and supporting information.
      • Budnitz D.S.
      • Pollock D.A.
      • Weidenbach K.N.
      • Mendelsohn A.B.
      • Schroeder T.J.
      • Annest J.L.
      National surveillance of emergency department visits for outpatient adverse drug events.
      • Jhung M.A.
      • Budnitz D.S.
      • Mendelsohn A.B.
      • Weidenbach K.N.
      • Nelson T.D.
      • Pollock D.A.
      Evaluation and overview of the National Electronic Injury Surveillance System—Cooperative Adverse Drug Event Surveillance Project (NEISS–CADES).
      Clinical narratives, diagnoses, testing, treatments, and up to two implicated medications are reported. The NEISS–AIP special study on self-directed violence characterizes self-directed violence–related emergency department visits by analyzing additional data reported by NEISS coders, including (1) whether the emergency department visit resulted from suicidal behavior or self-harm behavior; (2) existing medical and psychiatric conditions of the patient (e.g., clinical depression, alcohol abuse, or substance abuse) as reported by relatives or friends; and (3) alcohol or drug use at the time of the injury as determined by hospital staff members or laboratory reports.
      CDC
      Nonfatal self-inflicted injuries among adults aged ≥65 years—U.S., 2005.
      For ingestions involving self-directed violence, up to four implicated products and the amount ingested are reported.

      Case Definition

      A case was defined as an emergency department visit by a patient from January 1, 2006, to December 31, 2007, for an overdose of an acetaminophen-containing product. A medication overdose was defined as ingestion of supra-therapeutic amounts or inadvertent exposure. Acetaminophen-containing products were identified based on verbatim names of implicated medications. When nonspecific brand names were reported, cases were included only if all available formulations contained acetaminophen. Cases in which the emergency department chart described abuse/recreational use of acetaminophen products or in which there was insufficient information to characterize the event were not included.

      Measures

      An emergency department visit for acetaminophen overdose was the primary outcome measure. Unintentional overdoses were categorized as unsupervised ingestions or therapeutic misadventures. Unsupervised ingestions included consumption of medication by a child aged ≤10 years without adult supervision. Therapeutic misadventures included overuse of a drug for medicinal effects (e.g., ingestion of greater-than-recommended quantities for control of pain or fever, or intentional use of a medication prescribed for someone else) and medication errors (e.g., unintentional ingestions of greater-than-recommended quantities because of mistakes in administration, prescribing, or dispensing). Secondary measures included patient age; gender; emergency department treatments; disposition from the emergency department; and type, dose form, and number of acetaminophen-containing pills ingested.

      Statistical Analysis

      Each NEISS–CADES and NEISS–AIP visit was assigned a sample weight based on the inverse probability of selection, and adjusted annually for nonresponse, population changes, hospital closures, and mergers.
      U.S. Consumer Product Safety Commission
      National Electronic Injury Surveillance System—all injury program sample design and implementation.
      National estimates of emergency department visits from 2006 to 2007 and the corresponding 95% CIs were calculated in 2009–2010 using the Surveymeans procedure in SAS, version 9.2, to account for weighting and the complex sample design. To obtain annual estimates, frequency estimates and 95% CIs were divided by 2 for the period 2006–2007. Population rates were calculated using 2006 and 2007 population estimates from the U.S. Census Bureau.
      DHHS, CDC, National Center for Health Statistics (NCHS)
      Bridged-Race Population Estimates, U.S. July 1st resident population by state, county, age, sex, bridged-race, and Hispanic origin, compiled from 1990–1999 bridged-race intercensal population estimates and 2000–2008 (Vintage 2008) bridged-race postcensal population estimates. CDC WONDER On-line Database.
      National estimates based on <20 cases or with a coefficient of variation >30% were considered statistically unstable and are not reported.
      • Schroeder T.J.
      • Ault K.
      National Electronic Injury Surveillance System (NEISS) sample design and implementation from 1997 to present.

      Results

      Based on 2717 total cases, an estimated 78,414 emergency department visits (95% CI=63655, 93172 visits) occurred annually for overdoses of acetaminophen-containing products, excluding overdoses related to recreational drug use or abuse. Most emergency department visits for overdoses of acetaminophen-containing products (69.8%, 95% CI=66.4%, 73.2%) involved self-directed violence; the remaining visits (30.2%, 95% CI=26.8%, 33.6%) involved unintentional overdoses. Unintentional overdoses included unsupervised ingestions by a child (13.4% of the total, 95% CI=11.0%, 15.9%) and therapeutic misadventures (16.7% of the total, 95% CI=14.0%, 19.5%).
      The median age of individuals treated for self-directed violence involving acetaminophen was less than the median age for therapeutic misadventures (29 years, range=10–85 years, vs 35 years, range=<1–93 years). For unsupervised child ingestions, the median age was 2 years (range=<1–10 years). Most visits for self-directed violence and therapeutic misadventures were made by women/girls (65.9% and 63.5%, respectively); most visits for unsupervised ingestions were by men/boys (55.6%; Table 1). Nearly three fourths of self-directed violence visits involving acetaminophen required admission/observation in an acute care facility (45.2%) or admission to a psychiatric service or facility (28.9%). Most emergency department visits for unsupervised ingestion and therapeutic misadventures involving acetaminophen did not require admission/observation, but 28.0% (95% CI=21.8%, 34.1%) of children treated for unintentional ingestion of an acetaminophen product were treated with N-acetylcysteine (NAC) or received gastrointestinal decontamination.
      Table 1Emergency department visits for overdoses involving acetaminophen-containing products, U.S., 2006–2007
      Patient and case characteristicsEmergency department visits for intentional overdoseEmergency department visits for unintentional overdose
      Self-directed violence
      Estimates based on the National Electronic Injury Surveillance System—All Injury Program, 2006–2007. Estimates based on <20 cases, a total estimate <1200, or with a coefficient of variation >30% are not shown (—).
      Unsupervised ingestion
      Estimates based on the National Electronic Injury Surveillance System—Cooperative Adverse Drug Event Surveillance project, 2006–2007. Estimates based on <20 cases, a total estimate <1200, or with a coefficient of variation >30% are not shown (—).
      Therapeutic misadventures
      Estimates based on the National Electronic Injury Surveillance System—Cooperative Adverse Drug Event Surveillance project, 2006–2007. Estimates based on <20 cases, a total estimate <1200, or with a coefficient of variation >30% are not shown (—).
      ,
      Therapeutic misadventures includes intentional ingestion of greater than recommended quantities for therapeutic effects and unintentional ingestions of greater than recommended quantities because of medication errors. Cases of abuse (recreational use or use for euphoric effects) are not included.
      Cases No.Annual national estimateCases No.Annual national estimateCases No.Annual national estimate
      No.% (95% CI)No.% (95% CI)No.% (95% CI)
      Age (years)
       <6NANANA43910,46399.2 (98.4, 100.0)10
       6–141052,4404.5 (3.1, 5.8)623
       15–2471619,64135.9 (31.6, 40.1)NANANA1113,41826.0 (21.0, 31.1)
       25–3955516,42430.0 (26.7, 33.4)NANANA1093,51726.8 (22.0, 31.6)
       40–492919,21716.8 (14.9, 18.8)NANANA451,33510.2 (6.8, 13.6)
       50–641575,81210.6 (8.0, 13.2)NANANA672,31317.6 (13.0, 22.2)
       >64331,2112.2 (1.4, 3.1)NANANA501,91214.6 (9.5, 19.7)
      Gender
      Unknown for one case of therapeutic misadventure
       Women/girls122536,07165.9 (62.1, 69.6)2034,68044.4 (37.6, 51.2)2658,34063.5 (56.4, 70.7)
       Men/boys63218,67234.1 (30.4, 37.9)2425,86655.6 (48.8, 62.4)1494,72136.0 (28.8, 43.1)
      Disposition
      Unknown for two cases of self-directed violence
       Admitted, admitted for observation, or transferred to another acute care facility78124,72245.2 (37.7, 52.6)641113,54027.0 (19.9, 34.1)
       Admitted to psychiatric facility or service55615,83028.9 (23.3, 34.5)NANANANANANA
       Treated and released or left against medical advice51814,17125.9 (19.6, 32.2)3819,60391.1 (85.2, 96.9)3049,58573.0 (65.9, 80.1)
      Other implicated medications
       Non-acetaminophen products also involved95528,86052.7 (46.5, 59.0)451143,94930.1 (24.1, 36.1)
       Only acetaminophen products involved90225,88347.3 (41.0, 53.5)4009,95394.4 (91.4, 97.3)3019,17569.9 (63.9, 75.9)
      Number of acetaminophen products
       One acetaminophen product involved175351,36193.8 (92.2, 95.4)43910,42998.9 (97.7, 100.0)39312,54395.6 (93.3, 97.8)
       ≥2 acetaminophen products involved1043,3836.2 (4.6, 7.8)622
      Acetaminophen product classes
       Single-ingredient acetaminophen82120,88538.2 (33.1, 43.2)3057,09967.3 (61.3, 73.3)1233,37825.7 (19.4, 32.1)
       Opioid analgesic combination72924,37144.5 (39.5, 49.5)691,62515.4 (10.1, 20.7)2057,25855.3 (48.4, 62.2)
       Non-opioid analgesic combination812,3834.4 (2.8, 5.9)26308486.5 (3.9, 9.0)
       Cough/cold/antihistamine combination1625,1299.4 (7.1, 11.6)401,11210.5 (6.3, 14.8)421,31910.1 (7.3, 12.8)
       Two or more different acetaminophen product classes641,9763.6 (2.5, 4.7)515
       Total185754,743100.044510,546100.041513,125100.0
      a Estimates based on the National Electronic Injury Surveillance System—All Injury Program, 2006–2007. Estimates based on <20 cases, a total estimate <1200, or with a coefficient of variation >30% are not shown (—).
      b Estimates based on the National Electronic Injury Surveillance System—Cooperative Adverse Drug Event Surveillance project, 2006–2007. Estimates based on <20 cases, a total estimate <1200, or with a coefficient of variation >30% are not shown (—).
      c Therapeutic misadventures includes intentional ingestion of greater than recommended quantities for therapeutic effects and unintentional ingestions of greater than recommended quantities because of medication errors. Cases of abuse (recreational use or use for euphoric effects) are not included.
      d Unknown for one case of therapeutic misadventure
      e Unknown for two cases of self-directed violence
      Acetaminophen-containing products were the only drugs implicated in most emergency department visits for unsupervised ingestions and therapeutic misadventures (94.4% and 69.9%, respectively); however, half (52.7%) of visits for self-directed violence involved at least one additional non-acetaminophen-containing drug. Visits in which more than one acetaminophen product was implicated were infrequent across all intent types. For intentional overdoses, more than one acetaminophen-containing product was implicated in only 6.2% of emergency department visits (104 cases). More than one acetaminophen-containing product was implicated in only six cases of unsupervised child ingestion and 22 cases of therapeutic misadventure. Of the emergency department visits for unsupervised ingestion, consumption of a pill or tablet form of acetaminophen (56.4%, 95% CI=50.8%, 62.0%) was most commonly reported. Consumption of a liquid acetaminophen product was reported in 37.0% (95% CI=31.6%, 42.3%) of emergency department visits for unsupervised ingestions, and the formulation consumed was unknown in 6.7% (95% CI=3.3%, 10.1%) of visits.
      Population rates of self-directed violence visits involving acetaminophen were highest among patients aged 15–24 years (46.4 per 100,000 individuals per year) and declined with increasing age (Figure 1). The second highest population rate of emergency department visits was for unsupervised ingestions among children aged <6 years (42.5 per 100,000 individuals per year). The population rates for emergency department visits attributed to therapeutic misadventures were 2.5- to 6.9-fold lower than the rates for self-directed violence for all age groups except among individuals aged >64 years.
      Figure thumbnail gr1
      Figure 1Estimated rates of emergency department visits for overdoses involving acetaminophen-containing products, by age category and intent—U.S., 2006–2007
      Note: Population rate estimates based on the average of 2006 and 2007 mid-year U.S. Census estimates from the National Center for Health Statistics, CDC; bars represent 95% CIs; asterisk denotes estimates with coefficient of variation >30%
      Population rates of self-directed violence visits were significantly higher for women/girls (27.2 per 100,000 individuals per year, 95% CI=21.9, 32.6) compared to men/boys (14.4 per 100,000 individuals per year, 95% CI=11.4, 18.0). The difference between men/boys and women/girls narrowed with increasing age (Figure 2). Disposition from the emergency department, involvement of non-acetaminophen products, and number and type of implicated acetaminophen-containing products did not differ significantly between men/boys and women/girls. Single-ingredient acetaminophen products were involved in most self-directed violence visits involving patients aged ≤24 years, whereas opioid analgesic combination products were most commonly implicated in self-directed violence visits involving patients aged ≥25 years (Appendix A, available online at www.ajpmonline.org).
      Figure thumbnail gr2
      Figure 2Estimated rates of emergency department visits for self-directed violence involving acetaminophen-containing products, by age category and gender—U.S., 2006–2007
      Note: Population rate estimates based on the average of 2006 and 2007 mid-year U.S. Census estimates from the National Center for Health Statistics, CDC; bars represent 95% CIs; asterisk denotes estimates with coefficient of variation >30%
      The amount of acetaminophen ingested was documented in 69.8% of the emergency department visits for self-directed violence. Among the self-directed violence visits in which the amount of acetaminophen product ingested was documented, 39.0% (95% CI=34.3%, 43.7%) involved ingestion of ≤10 acetaminophen-containing pills; 24.0% (95% CI=20.7%, 27.4%) involved ingestion of 11–20 pills; and 31.9% (95% CI=28.1%, 35.8%) involved ingestion of 21 or more pills (Table 2). In approximately 5% of self-directed violence visits, at least half a bottle of acetaminophen-containing product was consumed; however, the exact number of pills was not reported. Number of pills ingested did not vary significantly by age (Appendix A, available online at www.ajpmonline.org).
      Table 2Number of acetaminophen-containing pills ingested in cases resulting in emergency department visits for self-directed violence involving acetaminophen-containing products—U.S., 2006–2007
      Number of pillsAnnual national estimate
      Percents are based on 69.8% of visits in which the amount of acetaminophen product ingested was documented.
      %(95% CI)
      ≤1039.0(34.3, 43.7)
      11–2024.0(20.7, 27.4)
      21–3014.7(12.1, 17.3)
      31–404.8(3.2, 6.4)
      41–503.8(2.6, 5.1)
      ≥518.6(6.8, 10.3)
      ≥½ bottle5.1(3.1, 7.0)
      a Percents are based on 69.8% of visits in which the amount of acetaminophen product ingested was documented.
      Among emergency department visits for therapeutic misadventures, the type of acetaminophen product most commonly implicated differed significantly by age. In younger patients (those aged 15–24 years), the rate of visits for overdoses of non-opioid-containing acetaminophen products was three times higher than the rate for opioid-containing acetaminophen products (6.0 per 100,000 individuals per year, 95% CI=4.0, 7.9, vs 1.9 per 100,000 individuals per year, 95% CI=0.9, 2.9). For older patients (aged ≥40 years), the rate of emergency department visits related to use of opioid-containing acetaminophen products was four times higher than the rate of visits from non-opioid-containing products (3.3 per 100,000 individuals per year, 95% CI=2.1, 4.5, vs 0.8 per 100,000 individuals per year, 95% CI=0.3, 1.2).
      More than half of emergency department visits for therapeutic misadventures (56.1%, 95% CI=50.6%, 61.6%) resulted from overuse of an acetaminophen-containing product for medicinal effects (e.g., for added symptom relief), whereas only 16.3% (95% CI=21.6%, 33.5%) were attributed to medication errors. The specific circumstances were unknown for the remaining 27.6% of visits. Among those aged 15–24 years, overuse for medicinal effects was documented in 75.0% (95% CI=66.1%, 83.8%) of emergency department visits attributed to therapeutic misadventures.

      Discussion

      This is the first study that we are aware of that uses nationally representative surveillance data to describe non-abuse-related overdoses involving acetaminophen-containing products by patient intent, patient demographics, and type of acetaminophen product.

      Self-Directed Violence

      The finding that 70% of emergency department visits for non-abuse-related acetaminophen overdoses involved intentional self-harm and that nearly 75% of these visits resulted in medical or psychiatric hospitalization suggests that addressing self-directed violence has large potential for public health impact. Indeed, based on an annual estimate of 206,981 emergency department visits,
      CDC
      Web-based injury statistics query and reporting system (WISQARS) [Online]. National Center for Injury Prevention and Control, CDC (producer).
      one of every four emergency department visits for intentional self-poisoning involved an acetaminophen product.
      Adolescents and young adults, particularly women/girls, had the highest rate of self-directed violence visits for acetaminophen overdose, and OTC products were most commonly involved. Previous studies have found that ingestion of medications is a common method of suicide attempt among adolescents,
      CDC
      Fatal and nonfatal suicide attempts among adolescents—Oregon, 1988–1993.
      impulsivity is an important factor in self-poisoning by adolescents,
      • Kingsbury S.
      • Hawton K.
      • Steinhardt K.
      • James A.
      Do adolescents who take overdoses have specific psychological characteristics? A comparative study with psychiatric and community controls.
      and that acetaminophen self-poisonings are often impulsive acts.
      • Hawton K.
      • Ware C.
      • Mistry H.
      • et al.
      Paracetamol self-poisoning Characteristics, prevention and harm reduction.
      There is some evidence that restrictions on the amount of acetaminophen that may be purchased at one time have reduced acetaminophen-related self-harm in some localities,
      • Hawton K.
      • Townsend E.
      • Deeks J.
      • et al.
      Effects of legislation restricting pack sizes of paracetamol and salicylate on self-poisoning in the United Kingdom: before and after study.
      • Prince M.I.
      • Thomas S.H.
      • James O.F.
      • Hudson M.
      Reduction in incidence of severe paracetamol poisoning.
      but there is variable adherence to purchasing restrictions,
      • Greene S.L.
      • Dargan P.I.
      • Leman P.
      • Jones A.L.
      Paracetamol availability and recent changes in paracetamol poisoning: is the 1998 legislation limiting availability of paracetamol being followed?.
      and the long-term effectiveness of these measures in reducing acetaminophen-related harm continues to be debated.
      • Hawkins L.C.
      • Edwards J.N.
      • Dargan P.I.
      Impact of restricting paracetamol pack sizes on paracetamol poisoning in the United Kingdom: a review of the literature.
      • Prescott K.
      • Stratton R.
      • Freyer A.
      • Hall I.
      • Le Jeune I.
      Detailed analyses of self-poisoning episodes presenting to a large regional teaching hospital in the UK.
      Another option that has been suggested to discourage impulsive self-poisonings is packaging acetaminophen products in blister packs, and in at least one study of self-poisoning with acetaminophen, individuals who had taken medication from blister packs ingested substantially fewer pills.
      • Hawton K.
      • Ware C.
      • Mistry H.
      • et al.
      Paracetamol self-poisoning Characteristics, prevention and harm reduction.

      Unsupervised Ingestion

      The population rate of emergency department visits for unsupervised ingestions among children aged <6 years was second to only the rate of emergency department visits for self-directed violence by those aged 15–24 years, and nearly one third of unsupervised ingestions were treated with NAC or gastrointestinal decontamination. Similar to previous studies,
      • Chien C.
      • Marriott J.L.
      • Ashby K.
      • Ozanne-Smith J.
      Unintentional ingestion of over the counter medications in children less than 5 years old.
      • Schillie S.F.
      • Shehab N.
      • Thomas K.E.
      • Budnitz D.S.
      Medication overdoses leading to emergency department visits among children.
      most of these unsupervised ingestions were by children aged <6 years, and slightly more than half of emergency department visits for unsupervised ingestions of acetaminophen were attributed to ingestion of pills. These findings suggest that to eliminate morbidity from child ingestions, interventions will need to include liquid and pill formulations.
      Incorporating flow restrictors could reduce the amount of liquid medication that children are able to drink directly from the bottle and unit–dose packaging can limit the amount of product consumed in unsupervised ingestions.
      • Schoenewald S.
      • Kuffner E.
      Unit dose packaging may decrease amount of over-the-counter (OTC) medicine ingested following accidental unsupervised ingestions (AUIs) [NACCT abstract 271].
      Targeted education campaigns focusing on limiting child access to medicines could complement packaging innovations.

      Therapeutic Misadventure

      Therapeutic misadventures accounted for 16.7% of emergency department visits for acetaminophen overdoses, and most therapeutic misadventures (56.1%) involved overuse of an acetaminophen product for a medicinal effect. Previous studies of patient knowledge and practices have found that oftentimes, individuals are not aware of the potential harm from taking or administering acetaminophen improperly.
      • Myers W.C.
      • Otto T.A.
      • Harris E.
      • Diaco D.
      • Moreno A.
      Acetaminophen overdose as a suicidal gesture: a survey of adolescents' knowledge of its potential for toxicity.
      • Stumpf J.L.
      • Skyles A.J.
      • Alaniz C.
      • Erickson S.R.
      Knowledge of appropriate acetaminophen doses and potential toxicities in an adult clinic population.
      Among adolescents and young adults, overuse of an acetaminophen product for more potent medicinal effects was documented in three fourths of emergency department visits attributed to therapeutic misadventures, and three fourths of therapeutic misadventures involved OTC formulations. On the other hand, among older adults, more than four fifths of therapeutic misadventures involved acetaminophen–opioid combination products. Thus, these data suggest that to reduce the incidence of emergency department visits for therapeutic misadventures, interventions should target safe practices in the use of OTC medications by adolescents and young adults and safe use of acetaminophen–opioid combination products by older adults.

      Limitations

      The current findings should be interpreted in the context of the limitations of emergency department–based public health surveillance data. First, the current estimates likely underestimate the number of medication overdoses involving acetaminophen. Both NEISS–CADES and NEISS–AIP capture only those overdoses that are treated in a hospital emergency department and do not capture overdoses that are not treated in emergency departments or that result in death prior to an emergency department visit. A narrow definition for acetaminophen product exposure was used and included only cases in which an acetaminophen product was explicitly mentioned. Products that are available in non-acetaminophen-containing formulations (e.g., DayQuil®, hydrocodone) were not included. Emergency department visits related to abuse/recreational drug use are not included.
      Second, case identification relies on patients and caregivers to provide accurate accounts of the circumstances surrounding the overdose, physicians to correctly diagnose and document the medication overdose and to identify an acetaminophen product, and NEISS coders to correctly interpret and transcribe supporting case information. Although the number of pills ingested was collected for self-directed violence patients, the exact milligram dose was not collected. There also was potential for misclassification of intent, particularly when the circumstances surrounding the overdose are sensitive matters (e.g., intentional ingestions may have been reported by patients as mistakes or errors and inappropriately coded as unintentional ingestions).
      Third, when acetaminophen combination products or non-acetaminophen-containing products were implicated, it is possible that the pharmacologic effects of the non-acetaminophen drug precipitated the emergency department visit. Lastly, emergency department record–based surveillance data were used to estimate the public health burden of acetaminophen overdose but these data do not directly assess liver injury. Emergency department–based surveillance data, including data from NEISS, are not ideal for measuring the burden of acetaminophen-induced liver toxicity because acetaminophen may be implicated only after admission; reporting of diagnostic testing is not always complete; and although a patient may have sustained a serious overdose, toxicity may be averted by prompt treatment.

      Conclusion

      Non-abuse-related overdoses of acetaminophen-containing products are involved in many emergency department visits each year, particularly emergency department visits for self-directed violence. Nationally representative data on acetaminophen-related emergency department visits can help target interventions to have the greatest potential for minimizing harms while preserving options for pain management and symptom relief.

      Acknowledgments

      This investigation was funded by the CDC. We thank Kelly Weidenbach, MPH, Victor Johnson (Northrop–Grumman contractors for CDC), Lee Annest, PhD, and Tadesse Haileyesus, MS, of CDC, and Tom Schroeder, MS, Cathy Irish, BS, Joel Friedman, BA, and staff of the Division of Hazard and Injury Data Systems, U.S. Consumer Product Safety Commission for assistance with data collection and processing. We thank Nadine Shehab, PharmD, MPH, of CDC for assistance with programming and thoughtful contributions to the manuscript. All individuals named consented to be acknowledged and none have disclaimers to report.
      The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC.
      No financial disclosures were reported by the authors of this paper.

      Supplementary data

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