Introduction

Prescription medications are widely used to treat a variety of acute and chronic medical conditions, and their use has increased substantially in the United States over the past 20–25 years.¹ In the years 1988–1994, approximately 38 percent of the U.S. population reported that they had used a prescription drug in the past 30 days; this increased to nearly 48 percent of the population in the period from 2005 to 2008.² Prescription drug use has increased among all age groups, reaching 25 percent of children and 90 percent of the elderly in the years 2005–2008.³ Moreover, the number of medications per patient also has increased. For example, in the period from 1988–1994, just over one-third of the elderly used three or more prescription drugs in the past 30 days, compared to nearly two-thirds in the years 2005–2008.⁴

The intention of prescription medications is to help cure disease or alleviate symptoms; however, sometimes the drugs can cause patient injury, known as an adverse drug event (ADE). With the substantial rise in the use of medications, there has been a concomitant increase in the occurrence of ADEs reported to the FDA.⁵ However, the FDA's Adverse Event Reporting System only requires drug manufacturers to report ADEs while many ADEs are often reported in hospitals instead. Between 2004 and 2008, there was a 52 percent increase in the number of ADEs reported in U.S. hospitals.⁶ Adverse drug events increase the risk of death, the length of hospitalization, and the cost of care.^7,8

Hospital stays involving ADEs have been reported for a range of drugs, including hormones, analgesics, antibiotics, and cardiovascular drugs, among others.⁹ Adverse drug events may be a reason for admission to the hospital—that is, the ADE was present on admission (POA). Alternatively, ADEs may originate during the hospital stay because of medications administered during hospitalization. Adverse drug events are the most common nonsurgical adverse events in hospitals.¹⁰ In 2008, about 14 percent of Medicare patients experienced an adverse event originating during their hospital stay, costing an estimated $3.8 billion a year, with about a third of the events being ADEs.¹¹ This Statistical Brief presents more recent data on national ADE rates over all payers in 2011.

In 32 of 46 States participating in the Healthcare Cost and Utilization Project (HCUP), the data indicate whether diagnoses are POA or originate during the hospital stay. In these States, inpatient data can be used to chart the frequency of in-hospital events and to report the frequency of community-occurring ADEs that are serious enough to require hospitalization and be observed at admission. This Statistical Brief presents data from these 32 States. The 2011 rates are reported for general classes as well as the specific types of drugs that cause ADEs.¹²

All numbers noted in the text and included in the tables are actual values, not estimates, because the data include a census of discharges rather than a sample of discharges. In other words, we count the actual number of hospital stays with ADEs in the 32 States. Because we analyze numbers for the actual population rather than a sample, there is no need to estimate how well the sample represents an underlying population. As a result, there is no sampling error associated with the calculated values presented, and significance testing is not necessary.¹³

Findings

Frequency of adverse drug events, 2011

Across a total of 20,172,966 discharges in the 32 States included in our analysis, there were 782,757 ADEs that were present on admission and 259,662 ADEs that originated during the hospital stay. Table 1 presents the rate and percentage of ADEs for a range of causes. Overall, ADEs observed during hospitalization were more likely to be present on admission (388 per 10,000 discharges) than to originate during the hospital stay (129 per 10,000 discharges). Among ADEs present on admission, the most common general causes were antibiotics and anti-infectives (23.4 percent of all ADEs), systemic agents (13.6 percent), nonspecific ADE causes (12.9 percent), and hormones (11.9 percent). Among ADEs that originated during the stay, the most prevalent general causes were antibiotics and anti-infectives (28.0 percent of all ADEs), nonspecific ADE causes (16.6 percent), hormones (16.1 percent), and analgesics (12.6 percent).

Table 1

Adverse drug events (ADEs) in hospital inpatient settings, 32 states, 2011.

General causes of adverse drug events, 2011

The general causes of adverse drug events that were present on hospital admission and those that originated during the stay are provided in Figure 1. The order of the list is from the most to least frequently occurring cause overall. The most frequent general causes of ADEs were antibiotics and anti-infectives (127 events per 10,000 discharges), nonspecific ADE causes (71 events), hormones (67 events), and analgesics (62 events). Across all general causes, ADEs were substantially more likely to be present on admission than to originate during the stay.

Figure 1

General causes of adverse drug events (ADEs), 2011. Source: Agency for Healthcare Research and Quality (AHRQ), Center for Delivery, Organization, and Markets, Healthcare Cost and Utilization Project (HCUP), State Inpatient Databases (SID) for 32 States, (more...)

Most common specific causes of adverse drug events, 2011

Figure 2 presents the 10 most common specific causes of adverse drug events. The data represent causes that occurred at a rate of more than 15 per 10,000 discharges. Clostridium difficile infection was the most common ADE cause, occurring at a rate of 95 per 10,000 discharges. The next two most frequently occurring ADE causes—antineoplastic drugs and steroids—each occurred at a rate of 57 per 10,000 discharges.

Figure 2

Ten most common specific causes of adverse drug events (ADEs), 2011. Abbreviation: NSAIDS, nonsteroidal anti-inflammatory drugs Source: Agency for Healthcare Research and Quality (AHRQ), Center for Delivery, Organization, and Markets, Healthcare Cost (more...)

With the exception of antibiotics, all of the most common specific causes of ADEs were more likely to be present on admission than to originate during the hospital stay. For antibiotics, the number of events was nearly equal across the settings: 12.5 ADEs per 10,000 discharges were present on admission versus 12.9 ADEs that originated during the stay.

Most common causes of adverse drug events that were present on admission versus originated during the stay, 2011

Across all causes of adverse drug events, there were three times as many ADEs that were present on admission than originated during the stay. Most causes of adverse drug events were more likely to be present on admission.

Figure 3 presents the ratio of ADEs per 10,000 discharges that were present on admission versus those that originated during the stay for ADE causes that had at least a 5-fold difference (i.e., the ratio was at least 5.0). Most of the ADE causes had a ratio between 5.0 and 10.0. Only two ADE causes exceeded a ratio of 10.0: ADEs that were due to antidepressants (17.6 times more likely to be POA) and central nervous system drugs (13.5 times more likely to be POA).

Figure 3

Most common causes of adverse drug events (ADEs) that were present on admission versus those that originated during the stay, 2011. Abbreviation: NSAIDS, nonsteroidal anti-inflammatory drugs Source: Agency for Healthcare Research and Quality (AHRQ), Center (more...)

Only one ADE cause—CNS depressants and anesthetics (data not shown)—was more likely to originate during the hospital stay (4 per 10,000 discharges were present on admission versus 7 per 10,000 discharges originated during the stay). ADEs caused by antibiotics were about equally likely to originate during the stay as to be present on admission (data not shown).

Data Source

The estimates in this Statistical Brief are based upon data from the Healthcare Cost and Utilization Project (HCUP) 2011 State Inpatient Databases (SID) from 32 States. These States included data elements that designated whether diagnoses were present on admission or originated during the stay: Arkansas, Arizona, California, Colorado, Florida, Georgia, Hawaii, Iowa, Illinois, Indiana, Kansas, Kentucky, Massachusetts, Maryland, Michigan, Minnesota, Montana, Nebraska, New Jersey, Nevada, New York, Oklahoma, Oregon, Pennsylvania, South Carolina, South Dakota, Tennessee, Texas, Virginia, Vermont, Washington, and Wisconsin.

Definitions

The specific causes of adverse drug events presented in this Statistical Brief were based on a review of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes and external cause of injury codes (E codes). The specific ICD-9-CM codes used for each ADE cause is provided in the separate appendix associated with this Statistical Brief on the HCUP-US website at: http://www.hcup-us.ahrq.gov/reports/statbriefs/sb158_appendix.pdf.

Present on admission was determined for each discharge diagnosis based on two types of present-on-admission indicator flags in the SID: (1) a diagnosis-specific flag that indicates whether each diagnosis was present on admission, and (2) an E code flag that indicates whether each external cause of injury was present on admission.

A total of 4,554 hospitals and 30,149,145 discharges were in the original SID for the 32 States in this study. Hospitals and individual discharge records with missing or incomplete present-on-admission information were excluded from the analysis, as shown in Table 2.

Table 2

Exclusion criteria and the number of hospitals and discharges excluded.

The final analysis file for this Statistical Brief included 2,737 hospitals (60.1 percent) and 20,172,966 discharges (66.9 percent) across the 32 States.

For More Information

For more information about HCUP, visit http://www.hcup-us.ahrq.gov/.

For additional HCUP statistics, visit HCUPnet, our interactive query system, at http://hcupnet.ahrq.gov/.

For information on other hospitalizations in the United States, download HCUP Facts and Figures: Statistics on Hospital-Based Care in the United States in 2009, located at http://www.hcup-us.ahrq.gov/reports.jsp.

For a detailed description of HCUP, more information on the design of the State Inpatient Databases (SID), please refer to the following publications:

Introduction to the HCUP State Inpatient Databases. Online. December 2012. U.S. Agency for Healthcare Research and Quality. http://hcup-us.ahrq.gov/db/state/siddist/Introduction_to_SID.pdf. Accessed June 24, 2013.

APPENDIX. List of Adverse Drug Event Causes with Constituent ICD-9-CM Codes and Descriptions

About the SID The HCUP State Inpatient Databases (SID) are hospital inpatient databases from data organizations participating in HCUP. The SID contain the universe of the inpatient discharge abstracts in the participating HCUP States, translated into a uniform format to facilitate multistate comparisons and analyses. Together, the SID encompass more than 95 percent of all U.S. community hospital discharges in 2011. The SID can be used to investigate questions unique to one State, to compare data from two or more States, to conduct market area variation analyses, and to identify State-specific trends in inpatient care utilization, access, charges, and outcomes.

Suggested Citation Weiss AJ (Truven Health Analytics), Elixhauser A (AHRQ), Bae J (Emory University), Encinosa W (AHRQ). Origin of Adverse Drug Events in U.S. Hospitals, 2011. HCUP Statistical Brief #158. July 2013. Agency for Healthcare Research and Quality, Rockville, MD. http://www​.hcup-us.ahrq​.gov/reports/statbriefs/sb158.pdf.

Acknowledgments The authors would like to acknowledge the contributions of Devi Katikineni and Valeriy Bakaushin of Social & Scientific Systems, Inc.