Adverse Drug Events in Hospitalized Cardiac Patients

Adverse Drug Events in Hospitalized Cardiac Patients John Fanikos, RPh, MBAa, Jennifer L. Cina, PharmDa, Steven Baroletti, PharmD, MBAa, Karen Fiumara, PharmDa, Lina Matta, PharmDa, and Samuel Z. Goldhaber, MDb,* Little information is available concerning adverse drug events (ADEs) in cardiac patients. Therefore, the investigators report the results of cardiac patients in an ADE surveillance program, with the intent of reducing the frequency of future events. All reported adverse drug reactions and medication errors in cardiac patients over a 5-year period at Brigham and Women’s Hospital were reviewed. There were 547 ADEs in cardiac patients, a rate of 1.9 events for every 100 patient admissions. Preventable ADEs most often occurred during medication administration (34.2%), with wrong rate or frequency of medication administration the most widespread event. Cardiovascular agents (29.8%), anticoagulants (28.5%), and antimicrobial agents (10.8%) were the most common drug classes associated with ADEs. Injury or prolonged hospitalization occurred in 5.3% of patients. ADEs occurred most frequently on the admission day, on weekdays, and in the early morning hours. Peak frequencies of ADEs coincided with nursing shift changes. In conclusion, ADEs occur often in hospitalized cardiac patients and affect 2 of every 100 patient admissions. Given the high percentage of ADEs associated with drug administration, more resources should be directed at this step of medication use. Focusing interventions around nursing shift changes may further enhance preventive strategies. © 2007 Elsevier Inc. All rights reserved. (Am J Cardiol 2007;100:1465–1469) Medication errors and adverse drug reactions cause patient harm, incur cost, generate adverse publicity, compromise patient trust, and demoralize hospital staff members.1–7 Analysis of these events in cardiac patients has been limited.8 –12 We report here our rate of medication errors and adverse drug reactions in hospitalized cardiac patients at Brigham and Women’s Hospital (BWH; Boston, Massachusetts). We have determined the incidence, timing, and severity of errors; the medication classes involved; and the steps of care at which they occurred. Methods and Results BWH is a 747-bed tertiary care facility with 71 beds dedicated to adult cardiology and 51 beds dedicated to adult cardiac surgical patients. The hospital relies on physicians, nurses, and pharmacists to voluntarily report medication errors and adverse drug reactions by logging them into the hospital’s computer system at the time of occurrence. Event reporting is a voluntary process but is not anonymous. When an event is reported, our patient safety personnel immediately investigate, confirm all details, identify contributing factors, and propose system or process changes when necessary. We also use pharmacists deployed on patient care teams to identify and report events. We reviewed all adverse drug events (ADEs), defined as adverse drug reactions and medication errors, reported in cardiology and cardiac surgery patients from September 1, 1999, to September 30, 2004. We defined an adverse drug Departments of aPharmacy and bMedicine, Brigham and Women’s Hospital, Boston, Massachusetts. Manuscript received March 12, 2007; revised manuscript received and accepted June 10, 2007. *Corresponding author: Tel: 617-732-7566; fax: 617-264-5144. E-mail address: [email protected] (S.Z. Goldhaber). 0002-9149/07/$ – see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2007.06.041

reaction as a response to a drug that was noxious and unintended and that occurred at doses normally used for prophylaxis, diagnosis, or therapy of disease.13 A medication error was defined as an event that caused or led to inappropriate medication use or patient harm.13 All medication errors were considered preventable. We identified 547 ADEs: 1.9 events for every 100 patient admissions or 3.1 events for every 1,000 patient-days (Table 1). The numbers of adverse drug reactions and medication errors were similar, 274 (50.1%) and 273 (49.9%), respectively. Collectively, ADEs were associated with injury or prolonged hospitalization in 5.3% of patients. Our Drug Safety Committee scored 361 (66.0%) of these events as preventable. The medication administration step (187 [34.2%]) of the medication use process was most commonly associated with preventable ADEs, followed by transcription (61 [11.2%]), provider prescribing (57 [10.4%]), dispensing (27 [4.9%]), and monitoring (26 [4.8%]). When adverse drug reactions occurred, the most common drug classes associated with these events were anticoagulants (78 [28.5%]), followed by cardiovascular agents (77 [28.1%]) and analgesics or sedatives (31 [11.3%]) (Table 2). Anticoagulants were most often associated with elevations in laboratory monitoring tests (34 [12.4%]), thrombocytopenia (27 [9.9%]), and hemorrhage (17 [6.2%]). Cardiovascular agents produced electrolyte imbalances (16 [5.8%]), extravasation (15 [5.5%]), and hypotension (11 [4.0%]). Allergic reactions, such as hives, rash, or angioedema (15 [5.5%]) with antibiotics and oversedation (24 [8.8%]) with analgesics, were common reactions. The most common medication classes involved with errors were cardiovascular agents (86 [31.5%]), anticoagulants (55 [20.1%]), and antibiotics (30 [11.0%]) (Table 3). The most common error type was wrong frequency or rate of medication administration (29.7%), wrong dose (13.9%), www.AJConline.org

0 (0%) 11 (4.0%) 1 (0.4%) 1 (0.4%) 1 (0.4) 0 (0%) 1 (0.4%) 15 (5.5%) 0 (0%) 15 (5.5%) 0 (0%) 0 (0%) 1 (0.4) 0 (0%) 0 (0%) 16 (5.8%) 0 (0%) 16 (5.8%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 16 (5.8%) 0 (0%) 9 (3.3%) 2 (0.7%) 5 (1.8%) 0 (0%) 0 (0%) 3 (1.1%) 19 (6.9%) 17 (6.2%) 0 (0%) 1 (0.4%) 0 (0%) 0 (0%) 6 (2.2%) 0 (0%) 24 (8.8%) 0 (0%) 0 (0%) 24 (8.8%) 0 (0%) 0 (0%) 0 (0%) 4 (1.5%) 28 (10.2%) 27 (9.9%) 0 (0%) 0 (0%) 1 (0.4%) 0 (0%) 2 (0.7%) 1 (0.4%) 31 (11.3%) 0 (0%) 9 (3.3%) 0 (0%) 15 (5.5%) 0 (0%) 1 (0.4%) 8 (2.9%) 33 (12.0%) 34 (12.4%) 0 (0%) 0 (0%) 0 (0%) 11 (4.0%) 1 (0.4%) 1 (0.4%) 47 (17.2%) Anticoagulants Cardiovascular Analgesics and sedatives Antibiotics Electrolytes Antiplatelet All others Total

Arrhythmia/ Hypotension Extravasation Electrolyte Imbalance Renal or Hepatic Dysfunction Hemorrhage Oversedation/ Mental Status Change Thrombocytopenia Rash/Hives/ Angioedema

missed or omitted medication doses (12.8%), or wrong time (9.5%). When all adverse drug reactions and medication errors were combined, the most frequent consequence was temporary harm requiring intervention 229 (41.9%) (Table 4). These events were most commonly associated with cardiovascular agents (63 [11.5%]) and anticoagulants (61 [11.2%]). This was followed by the need for increased monitoring using blood chemistries, coagulation parameters, and vital signs (146 [26.7%]). Culprit agents that were associated with prolonged hospitalization, permanent patient harm, or near death were widespread, with 23 medications producing 29 events. Anticoagulation-associated hemorrhage and cardiovascular agent–induced cardiac arrhythmias were the most common causes of prolonged hospitalization. Permanent harm or near death were the result of adverse drug reactions to heparin (heparin-induced thrombocytopenia with thrombosis and subsequent amputation), amiodarone (hyperthyroidism), phenytoin (asystole), and furosemide (hearing loss). Preventable ADEs occurred most frequently in the early days of hospitalization, with 93 (25.7%) of preventable events occurring on the admission day and hospital day 1. ADEs occurred more frequently overall on weekdays than on weekends, with 104 (19.0%) on Tuesdays and 103 (18.8%) on Mondays, compared with 51 (9.3%) on Saturdays and 61 (11.2%) on Sundays. When the preventable events were adjusted for patient days, ADEs remained most common on Mondays and Tuesdays. The largest number of preventable events occurred in the morning hours, from 7 to 9 A.M., coinciding with the largest volume of medication dispensed. Peaks in preventable events also were more common around the times of nursing shift change (Figure 1). The highest rate of ADEs per medication dispensed occurred in the early morning hours, from 1 to 3 A.M. This period corresponds to our smallest volume of daily medication administration.

Other

274 (50.1%) 273 (49.9%) 547 (100%) 186 (34.0%) 361 (66.0%) 187 (34.2%) 61 (11.2%) 57 (10.4%) 27 (4.9%) 26 (4.8%) 3 (0.5%) 28,967 1.9 1.2 174,582 3.1 2.1

Elevated Laboratory Monitoring Test

Adverse drug reactions Medication errors Total ADEs Nonpreventable ADEs Preventable ADEs Administration errors or omissions Transcription failures Prescribing errors Dispensing errors Monitoring lapses Policy/procedure violations Total admissions Event rate per 100 admissions Preventable event rate per 100 admissions Patient-days Event rate per 1,000 patient-days Preventable event rate per 1,000 patient-days

Total

Table 2 Types of adverse drug reactions in cardiac patients

ADEs

Total

Table 1 Adverse drug event frequency and preventability in cardiac patients (n ⫽ 547)

0 (0%) 78 (28.5%) 17 (6.2%) 77 (28.1%) 3 (1.1%) 31 (11.3%) 7 (2.6%) 29 (10.6%) 0 (0%) 13 (4.7%) 0 (0%) 10 (3.6%) 18 (6.6%) 36 (13.1%) 45 (16.4%) 274 (100%)

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Table 3 Medication errors in cardiac patients Anticoagulants

Antibiotics

Analgesics and Sedatives

Electrolytes

Antiplatelet

Thrombolytics

All Others

Total

34 (12.5%) 8 (2.9%) 12 (4.4%) 8 (2.9%) 3 (1.1%) 3 (1.1%) 4 (1.5%) 1 (0.4%) 3 (1.1%) 1 (0.4%) 0 (0%) 1 (0.4%) 8 (2.9%) 86 (31.5%)

23 (8.4%) 6 (2.2%) 7 (2.9%) 2 (0.7%) 5 (2.6%) 1 (0.4%) 3 (1.1%) 3 (1.1%) 1 (0.4%) 1 (0.4%) 1 (0.4%) 0 (0%) 2 (0.7%) 55 (20.1%)

7 (2.6%) 1 (0.4%) 7 (2.6%) 7 (2.6%) 1 (0.4%) 2 (0.7%) 0 (0%) 0 (0%) 0 (0%) 1 (0.4%) 1 (0.4%) 0 (0%) 3 (1.1%) 30 (11.0%)

4 (1.5%) 5 (1.8%) 0 (0%) 0 (0%) 2 (0.7%) 0 (0%) 1 (0.4%) 0 (0%) 1 (0.4%) 0 (0%) 1 (0.4%) 0 (0%) 6 (2.2%) 20 (7.3%)

1 (0.4%) 5 (1.8%) 2 (0.7%) 1 (0.4%) 2 (0.7%) 5 (1.8%) 1 (0.4%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 2 (0.7%) 19 (7.0%)

5 (2.6%) 0 (0%) 1 (0.4%) 3 (1.1%) 2 (0.7%) 0 (0%) 0 (0%) 1 (0.4%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (0.4%) 13 (4.8%)

1 (0.4%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (0.4%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 2 (0.7%)

6 (2.2%) 13 (4.8%) 6 (2.2%) 5 (1.8%) 7 (2.6%) 2 (0.8%) 1 (0.4%) 2 (0.7%) 1 (0.4%) 1 (0.4%) 0 (0%) 0 (0%) 4 (1.5%) 48 (17.6%)

81 (29.7%) 38 (13.9%) 35 (12.8%) 26 (9.5%) 22 (8.1%) 14 (5.1%) 10 (3.7%) 7 (2.7%) 6 (2.2%) 4 (1.5%) 3 (1.1%) 1 (0.4%) 26 (9.5%) 273 (100%)

Table 4 Adverse drug reaction and medication error event severity Severity Temporary harm, intervention required Increased monitoring, no harm Reached patient, no harm Prolonged hospitalization Permanent harm or near death Other Total

Cardiovascular

Anticoagulants

Antimicrobials

Analgesics and Sedatives

Electrolytes

Antiplatelet

Thrombolytics

Other

Total

63 (11.5%) 41 (7.5%) 25 (4.6%) 8 (1.5%) 2 (0.4%) 24 (4.4%) 163 (29.8%)

61 (11.2%) 42 (7.7%) 5 (0.9%) 5 (0.9%) 2 (0.4%) 18 (3.3%) 133 (24.3%)

24 (4.4%) 10 (1.8%) 20 (3.7%) 1 (0.2%) 0 (0%) 4 (0.7%) 59 (10.8%)

26 (4.8%) 14 (2.6%) 7 (1.5%) 2 (0.4%) 0 (0%) 2 (0.4%) 51 (9.3%)

8 (1.5%) 19 (3.5%) 1 (0.2%) 1 (0.2%) 0 (0%) 3 (0.6%) 32 (5.9%)

9 (1.6%) 6 (1.1%) 6 (1.1%) 2 (0.4%) 0 (0%) 0 (0%) 23 (4.2%)

0 (0%) 1 (0.2%) 1 (0.2%) 0 (0%) 0 (0%) 0 (0%) 2 (0.4%)

38 (6.9%) 13 (2.4%) 8 (1.5%) 5 (0.9%) 1 (0.2%) 19 (3.5%) 84 (15.4%)

229 (41.9%) 146 (26.7%) 73 (13.3%) 24 (4.4%) 5 (0.9%) 70 (12.8%) 547 (100%)

Miscellaneous/Adverse Drug Events in Cardiac Patients

Wrong frequency/rate Wrong dose Missed dose Wrong time Wrong drug Wrong technique Wrong patient Inadequate monitoring Extra dose Wrong route Allergy Equipment failure All other Total

Cardiovascular

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Figure 1. Preventable ADEs by time of day.

Discussion ADEs occur frequently in cardiac patients, with approximately 2 events for every 100 patient hospital admissions. Cardiovascular agents and anticoagulants were the drug classes most often associated with adverse drug reactions and medication errors. The largest number of preventable events occurred from 7 to 9 A.M. This is a common time of shift change at our institution and transfer of patient care among nurses. There is also an increased opportunity for medication errors due to increased medication dispensing and administration. The American Heart Association’s scientific statement on medication errors recommends improved error reporting, rational drug prescribing, computer technology advances, and the development of national prevention standards.14 Over the past 5 years, system improvements include new rules, regulations, practice standards, and guidelines.15,16 To date, however, studies in cardiovascular patients have been limited. One study analyzed medication errors intercepted by pharmacists and reported that 24 medication errors occurred per 100 admissions. Cardiovascular medications were involved in 41.2% of these errors.17 In a previous study at our hospital, the reported ADE rate was 6.5 events per 100 patient admissions, or 11.5 ADEs per 1,000 patient-days, and was higher than our current rate.18 Physician prescribing (39%) and drug administration (38%) were identified as the culprit steps of care, but the medication class most frequently involved was analgesics. The periods of hospital admission and patient transfer between acute and long-term care facilities are vulnerable periods for ADE occurrence.19,20 Failed communication and unavailable medical records cause unintended drug discontinuations, drug omissions, dose changes, and incorrect drug administration. There is also a relation between long work hours, sleep deprivation, and serious medical errors.8,21 Although 1 study reported a higher mortality rate in patients admitted to hospitals on weekends compared with

weekdays,22 we found that medications were more safely delivered on weekends. Nursing shifts on the weekends at BWH are 12-hour shifts and may provide fewer opportunities for errors related to the transfer of patient care. High-risk medications with narrow safety margins, such as intravenous anticoagulants, are associated with high potential for patient harm. We recently reported that “smart” infusion devices intercepted human programming errors associated with misplaced zeros and/or decimal points and reduced the opportunity for medication overdosing or underdosing.23 There are several limitations to our study. The reporting system at BWH is a Web-based vendor application that is accessible to all employees. Reporters are asked to provide patient information, specific details of safety events, severity, and any possible contributing factors or suggestions for the prevention of future events. We do not know what proportion of overall ADEs was captured with our voluntary reporting system. We recognize that we may have underreported more serious events and that our reported event rate may be lower than the actual event rate. We did not conduct a root-cause analysis on each reported event. Although nurses and pharmacists have been shown to provide an important “safety net” in intercepting and preventing ADEs, we did not investigate their role in errors of commission or further identify where responsibilities may have failed.24 Finally, we did not evaluate the impact of physician work hours, nursing staffing patterns, or patient disease acuity on these events.8,21,25 However, our data do provide a “real life” picture of ADEs that affect cardiac patients and likely patients at other facilities that care for similar patient populations. ADE review can be prompt, promote a rapid response, and remove barriers that compromise patient safety.26 1. Bates DW, Cullen DJ, Laird N, Petersen LA, Small SD, Servi D, Laffel G, Sweitzer BJ, Shea BF, Hallisey R, et al. Incidence of adverse drug events and potential adverse drug events. JAMA 1995;274:29 –34.

Miscellaneous/Adverse Drug Events in Cardiac Patients 2. Chyka PA. How many deaths occur annually from adverse drug reactions in the United States? Am J Med 2000;109:122–130. 3. Johnson JA, Bootman JL. Drug-related morbidity and mortality: a cost of illness model. Arch Intern Med 1995;155:1949 –1956. 4. Bates DW, Spell N, Cullen DJ, Burdick E, Laird N, Petersen LA, Small SD, Sweitzer BJ, Leape LL. The cost of adverse drug events in hospitalized patients. JAMA 1997;277:307–311. 5. Claussen DC, Pestotnik SL, Evans RS, Lloyd JF, Burke JP. Adverse events in hospitalized patients. Excessive length of stay, extra costs and attributable mortality. JAMA 1997;277:301–306. 6. Grant SM. Who’s to blame for tragic error. Am J Nurs 1999;99:9. 7. Brink S. 1995 best hospitals. Tragedy at Dana-Farber. US News World Rep 1995;119:53–56. 8. Landrigan CP, Rothschild JM, Cronin JW, Kaushal R, Burdick E, Katz J, Lilly CM, Stone PH, Lockley SW, Bates DW, Czeisler CA. Effect of reducing interns’ work on serious medical errors in intensive care units. N Engl J Med 2004; 351:1838 –1848. 9. Kaushal R, Bates DW, Landrigan C, McKenna KJ, Clapp MD, Federico F, Goldmann DA. Medication errors and adverse drug events in pediatric inpatients. JAMA 2001;285:2114 –2120. 10. Simpson JH, Lynch R, Grant J, Alroomi L. Reducing medication errors in the neonatal intensive care unit. Arch Dis Child Neonatal Ed 2004;89:480 – 482. 11. Mehta RH, Alexander JH, Van de Werf F, Armstrong PW, Peiper KS, Garg J, Califf R, Granger CB. Relationship of incorrect dosing of fibrinolytic therapy and clinical outcomes. JAMA 2005;293:1746 – 1750. 12. Fanikos J, Stapinski C, Kucher N, Koo S, Tsilimingras K, Goldhaber SZ. Medication errors associated with anticoagulant therapy in the hospital. Am J Cardiol 2004;94:532–535. 13. Nebeker JR, Barach P, Samore MH. Clarifying adverse drug events: a clinician’s guide to terminology, documentation, and reporting. Ann Intern Med 2004;140:795– 801. 14. Freedman JE, Becker RC, Adams JE, Borzak S, Jesse JL, Newby KL, O’Gara P, Pezzullo JC, Kerber R, Coleman B, et al. Medication errors in acute cardiac care: an American Heart Association Scientific Statement from the Council on Clinical Cardiology Subcommittee on Acute Cardiac Care, Council on Cardiopulmonary and Critical Care, Council on Cardiovascular Nursing, and Council on Stroke. Circulation 2002; 106:2623–2629.

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