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January 22, 1997, Vol 277, No. 4 >
ARTICLE | January 22, 1997

Adverse Drug Events in Hospitalized Patients: Title and subTitle BreakExcess Length of Stay, Extra Costs, and Attributable Mortality FREE

David C. Classen, MD, MS; Stanley L. Pestotnik, MS, RPh; R. Scott Evans, PhD; James F. Lloyd; John P. Burke, MD
[+] Author Affiliations

Reprints: David C. Classen, MD, MS, Department of Clinical Epidemiology, LDS Hospital, Eighth Avenue and C Street, Salt Lake City, UT 84143.


JAMA. 1997;277(4):301-306. doi:10.1001/jama.1997.03540280039031
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References

Objective.  —To determine the excess length of stay, extra costs, and mortality attributable to adverse drug events (ADEs) in hospitalized patients.

Design.  —Matched case-control study.

Setting.  —The LDS Hospital, a tertiary care health care institution.

Patients.  —All patients admitted to LDS Hospital from January 1, 1990, to December 31,1993, were eligible. Cases were defined as patients with ADEs that occurred during hospitalization; controls were selected according to matching variables in a stepwise fashion.

Methods.  —Controls were matched to cases on primary discharge diagnosis related group (DRG), age, sex, acuity, and year of admission; varying numbers of controls were matched to each case. Matching was successful for 71% of the cases, leading to 1580 cases and 20197 controls.

Main Outcome Measures.  —Crude and attributable mortality, crude and attributable length of stay, and cost of hospitalization.

Results.  —ADEs complicated 2.43 per 100 admissions to the LDS Hospital during the study period. The crude mortality rates for the cases and matched controls were 3.5% and 1.05%, respectively (P<.001). The mean length of hospital stay significantly differed between the cases and matched controls (7.69 vs 4.46 days; P<.001) as did the mean cost of hospitalization ($10010 vs $5355; P<.001). The extra length of hospital stay attributable to an ADE was 1.74 days (P<.001). The excess cost of hospitalization attributable to an ADE was $2013 (P<.001). A linear regression analysis for length of stay and cost controlling for all matching variables revealed that the occurrence of an ADE was associated with increased length of stay of 1.91 days and an increased cost of $2262 (P<.001). In a similar logistic regression analysis for mortality, the increased risk of death among patients experiencing an ADE was 1.88 (95% confidence interval, 1.54-2.22; P<.001).

Conclusion.  —The attributable lengths of stay and costs of hospitalization for ADEs are substantial. An ADE is associated with a significantly prolonged length of stay, increased economic burden, and an almost 2-fold increased risk of death.

REFERENCES

1 +
Johnson JA, Bootman JL.  Drug-related morbidity and mortality: a cost of illness model . Arch Intern Med . 1995;;155:1949-1956.
2 +
Talley RB, Laventurier MF.  Drug-induced illness . JAMA . 1974;;229:1043-1048.
3 +
Porter J, Jick H.  Drug-related deaths among medical inpatients . JAMA . 1977;;237:879-881.
4 +
Jick H.  Drugs—remarkably non-toxic . N Engl J Med . 1974;;291:824-828.
5 +
Caranasos GJ, Stewart RB, Cluff LE.  Drug-induced illness leading to hospitalization . JAMA . 1974;;228:713-717.
6 +
Miller RR.  Hospital admissions due to adverse drug reactions: a report from the Boston Collaborative Drug Surveillance Program . Arch Intern Med . 1974;;134:219-223.
7 +
Melmon KL.  Preventable drug reactions: causes and cures . N Engl J Med . 1971;;284:1361-1368.
8 +
Karch FE, Lasagna L.  Adverse drug reactions: a critical review . JAMA . 1975;;234:1236-1241.
9 +
Cluff LE, Caranasos GJ, Stewart RB.  Clinical problems with drugs . In: Smith LH, ed. Major Problems in Internal Medicine . Philadelphia, Pa: WB Saunders Co; 1975;:vol 5.
10 +
Leape LL, Brennan TA, Laird N, et al.  The nature of adverse events in hospitalized patients: results of the Harvard Medical Practice Study . N Engl J Med . 1991;;324:377-384.
11 +
Classen DC, Pestotnik SL, Evans RS, Burke JP.  Computerized surveillance of adverse drug events in hospital patients . JAMA . 1991;;266:2847-2851.
12 +
Kuperman G, Gardner RM, Pryor TA. The HELP System: A Dynamic Hospital Information System . New York, NY: Springer Verlag; 1990;.
13 +
Evans RS, Larsen RA, Burke JP, et al.  Computer surveillance of hospital-acquired infections and antibiotic use . JAMA . 1986;;256:1007-1011.
14 +
Classen DC, Pestotnik SL, Evans RS, Burke JP.  Description of a computerized adverse drug event monitor using a hospital information system . Hosp Pharm . 1992;;27:774, 776-779, 783.
15 +
Evans RS, Classen DC, Stevens LE, et al.  Using a hospital information system to assess the effects of adverse drug events .In: Safran C, ed. Proceedings From the Seventeenth Annual Symposium on Computer Applications in Medical Care . New York, NY: McGraw-Hill Inc; 1993;:161-165.
16 +
Classen DC. Assessing the Impact of Adverse Hospital Events on the Cost of Hospitalization and Other Patient Outcomes. Salt Lake City: University of Utah; 1993. Thesis.
17 +
The LDS Hospital nurse acuity system. In: Nursing Care Manual . Salt Lake City, Utah: LDS Hospital; 1990;.
18 +
Davis RB, Iezzoni LI, Phillips RS, et al.  Predicting in-hospital mortality: the importance of functional status information . Med Care . 1995;;33:906-921.
19 +
Van Ruiswyk J, Hartz A, Guse C, Sigmann P, Porth C, Buck K.  Nursing assessments: patient severity of illness . Nurs Manag . 1990;;23:44-48.
20 +
Whalen KL.  Level of nursing care required by the unstable angina patient . Crit Care Med . 1990;;18:505-508.
21 +
Lovett RB, Wagner L, McMillan S.  Validity and reliability of a pediatric hematology oncology patient acuity tool . J Pediatr Oncol Nurs . 1991;;8:122-130.
22 +
Meyer D. GRASP: A Patient Information and Workload Management System . Morgantown, NC: MCS; 1978;.
23 +
Standard Cost Manager: User's Guide. Cleveland, Ohio: Ernst and Whinney, Intermountain Health Care Inc; 1987.
24 +
Haley RW.  Measuring the cost of nosocomial infections: methods for estimating the economic burden on the hospital . Am J Med . 1991;;91:32S-38S.
25 +
Haley RW.  Cost benefit analysis of infection control programs . In: Bennett JV, Brachman PS, eds. Hospital Infections . 3rd ed. Boston, Mass: Little Brown & Co; 1992;:507-532.
26 +
Polissar L, Diehr P.  Regression analysis in health services research: the use of dummy variables . Med Care . 1982;;20:959-966.
27 +
Bates DW, Cullen DJ, Laird N, et al, for the ADE Prevention Study Group.  Incidence of adverse drug events and potential adverse drug events: implications for prevention . JAMA . 1995;;274:29-34.
28 +
Chrischilles EA, Segar ET, Wallace RB.  Selfreported adverse drug reactions and related resource use . Ann Intern Med . 1992;;117:634-640.
29 +
Schneider PJ, Gift MG, Lee YP, Rothermich EA, Sill BE.  Cost of medication related problems at a university hospital . Am J Health Syst Pharm . 1995;;52:2415-2418.
30 +
Evans RS, Pestotnik SL, Classen DC, Horn SD, Bass SB, Burke JP.  Preventing adverse drug events in hospitalized patients . Ann Pharmacother . 1994;;28:523-527.
31 +
Colley CA, Lucas LM.  Polypharmacy: the cure becomes the disease . J Gen Intern Med . 1993;;8:278-283.
32 +
Berwick DM.  Eleven worthy aims for clinical leadership of health system reform . JAMA . 1994;;272:797-802.
33 +
Knox RA, Mooney BC.  Hospital dosage mistakes not rare: past cases reveal medication errors . Boston Globe . (April 16) , 1995;:1.
34 +
Prince BS, Goetz CM, Rihn TL, Olsky M.  Drugrelated emergency department visits and hospital admissions . Am J Hosp Pharm . 1992;;49:1696-1700.
35 +
Bloom BS.  Direct medical costs of disease and gastrointestinal side effects during treatment for arthritis . Am J Med . 1988;;84:20-24.
36 +
Sloan FA, Gordon GS, Cocks DL.  Hospital drugformularies and the use of hospital services . Med Care . 1993;;31:851-867.
37 +
Evans RS, Pestotnik SL, Classen DC, Bass SB, Burke JP.  Prevention of adverse drug events through computerized surveillance . In: Frisse ME, ed. Proceedings From the Sixteenth Annual Symposium on Computer Applications in Medical Care . New York, NY: McGraw-Hill Inc; 1992;:437-441.
38 +
Pestotnik SL, Classen DC, Evans RS, Stevens LE, Burke JP.  Prospective surveillance of imipenem/ cilastatin use and associated seizures using a hospital information system . Ann Pharmacother . 1993;;27:497-501.
39 +
Evans RS, Classen DC, Pestotnik SL, Clemmer TP, Weaver LK, Burke JP.  A decision support tool for antibiotic therapy . In: Gardner RM, ed. Proceedings From the Nineteenth Annual Symposium on Computer Applications in Medical Care . Philadelphia, Pa: Hanley & Belfus; 1995;:651-655.
40 +
Powe NR, Griffiths RI.  The clinical-economic trial: promise, problems, and challenges . Control Clin Trials . 1995;;16:377-394.

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Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Johnson JA, Bootman JL.  Drug-related morbidity and mortality: a cost of illness model . Arch Intern Med . 1995;;155:1949-1956.
2 +
Talley RB, Laventurier MF.  Drug-induced illness . JAMA . 1974;;229:1043-1048.
3 +
Porter J, Jick H.  Drug-related deaths among medical inpatients . JAMA . 1977;;237:879-881.
4 +
Jick H.  Drugs—remarkably non-toxic . N Engl J Med . 1974;;291:824-828.
5 +
Caranasos GJ, Stewart RB, Cluff LE.  Drug-induced illness leading to hospitalization . JAMA . 1974;;228:713-717.
6 +
Miller RR.  Hospital admissions due to adverse drug reactions: a report from the Boston Collaborative Drug Surveillance Program . Arch Intern Med . 1974;;134:219-223.
7 +
Melmon KL.  Preventable drug reactions: causes and cures . N Engl J Med . 1971;;284:1361-1368.
8 +
Karch FE, Lasagna L.  Adverse drug reactions: a critical review . JAMA . 1975;;234:1236-1241.
9 +
Cluff LE, Caranasos GJ, Stewart RB.  Clinical problems with drugs . In: Smith LH, ed. Major Problems in Internal Medicine . Philadelphia, Pa: WB Saunders Co; 1975;:vol 5.
10 +
Leape LL, Brennan TA, Laird N, et al.  The nature of adverse events in hospitalized patients: results of the Harvard Medical Practice Study . N Engl J Med . 1991;;324:377-384.
11 +
Classen DC, Pestotnik SL, Evans RS, Burke JP.  Computerized surveillance of adverse drug events in hospital patients . JAMA . 1991;;266:2847-2851.
12 +
Kuperman G, Gardner RM, Pryor TA. The HELP System: A Dynamic Hospital Information System . New York, NY: Springer Verlag; 1990;.
13 +
Evans RS, Larsen RA, Burke JP, et al.  Computer surveillance of hospital-acquired infections and antibiotic use . JAMA . 1986;;256:1007-1011.
14 +
Classen DC, Pestotnik SL, Evans RS, Burke JP.  Description of a computerized adverse drug event monitor using a hospital information system . Hosp Pharm . 1992;;27:774, 776-779, 783.
15 +
Evans RS, Classen DC, Stevens LE, et al.  Using a hospital information system to assess the effects of adverse drug events .In: Safran C, ed. Proceedings From the Seventeenth Annual Symposium on Computer Applications in Medical Care . New York, NY: McGraw-Hill Inc; 1993;:161-165.
16 +
Classen DC. Assessing the Impact of Adverse Hospital Events on the Cost of Hospitalization and Other Patient Outcomes. Salt Lake City: University of Utah; 1993. Thesis.
17 +
The LDS Hospital nurse acuity system. In: Nursing Care Manual . Salt Lake City, Utah: LDS Hospital; 1990;.
18 +
Davis RB, Iezzoni LI, Phillips RS, et al.  Predicting in-hospital mortality: the importance of functional status information . Med Care . 1995;;33:906-921.
19 +
Van Ruiswyk J, Hartz A, Guse C, Sigmann P, Porth C, Buck K.  Nursing assessments: patient severity of illness . Nurs Manag . 1990;;23:44-48.
20 +
Whalen KL.  Level of nursing care required by the unstable angina patient . Crit Care Med . 1990;;18:505-508.
21 +
Lovett RB, Wagner L, McMillan S.  Validity and reliability of a pediatric hematology oncology patient acuity tool . J Pediatr Oncol Nurs . 1991;;8:122-130.
22 +
Meyer D. GRASP: A Patient Information and Workload Management System . Morgantown, NC: MCS; 1978;.
23 +
Standard Cost Manager: User's Guide. Cleveland, Ohio: Ernst and Whinney, Intermountain Health Care Inc; 1987.
24 +
Haley RW.  Measuring the cost of nosocomial infections: methods for estimating the economic burden on the hospital . Am J Med . 1991;;91:32S-38S.
25 +
Haley RW.  Cost benefit analysis of infection control programs . In: Bennett JV, Brachman PS, eds. Hospital Infections . 3rd ed. Boston, Mass: Little Brown & Co; 1992;:507-532.
26 +
Polissar L, Diehr P.  Regression analysis in health services research: the use of dummy variables . Med Care . 1982;;20:959-966.
27 +
Bates DW, Cullen DJ, Laird N, et al, for the ADE Prevention Study Group.  Incidence of adverse drug events and potential adverse drug events: implications for prevention . JAMA . 1995;;274:29-34.
28 +
Chrischilles EA, Segar ET, Wallace RB.  Selfreported adverse drug reactions and related resource use . Ann Intern Med . 1992;;117:634-640.
29 +
Schneider PJ, Gift MG, Lee YP, Rothermich EA, Sill BE.  Cost of medication related problems at a university hospital . Am J Health Syst Pharm . 1995;;52:2415-2418.
30 +
Evans RS, Pestotnik SL, Classen DC, Horn SD, Bass SB, Burke JP.  Preventing adverse drug events in hospitalized patients . Ann Pharmacother . 1994;;28:523-527.
31 +
Colley CA, Lucas LM.  Polypharmacy: the cure becomes the disease . J Gen Intern Med . 1993;;8:278-283.
32 +
Berwick DM.  Eleven worthy aims for clinical leadership of health system reform . JAMA . 1994;;272:797-802.
33 +
Knox RA, Mooney BC.  Hospital dosage mistakes not rare: past cases reveal medication errors . Boston Globe . (April 16) , 1995;:1.
34 +
Prince BS, Goetz CM, Rihn TL, Olsky M.  Drugrelated emergency department visits and hospital admissions . Am J Hosp Pharm . 1992;;49:1696-1700.
35 +
Bloom BS.  Direct medical costs of disease and gastrointestinal side effects during treatment for arthritis . Am J Med . 1988;;84:20-24.
36 +
Sloan FA, Gordon GS, Cocks DL.  Hospital drugformularies and the use of hospital services . Med Care . 1993;;31:851-867.
37 +
Evans RS, Pestotnik SL, Classen DC, Bass SB, Burke JP.  Prevention of adverse drug events through computerized surveillance . In: Frisse ME, ed. Proceedings From the Sixteenth Annual Symposium on Computer Applications in Medical Care . New York, NY: McGraw-Hill Inc; 1992;:437-441.
38 +
Pestotnik SL, Classen DC, Evans RS, Stevens LE, Burke JP.  Prospective surveillance of imipenem/ cilastatin use and associated seizures using a hospital information system . Ann Pharmacother . 1993;;27:497-501.
39 +
Evans RS, Classen DC, Pestotnik SL, Clemmer TP, Weaver LK, Burke JP.  A decision support tool for antibiotic therapy . In: Gardner RM, ed. Proceedings From the Nineteenth Annual Symposium on Computer Applications in Medical Care . Philadelphia, Pa: Hanley & Belfus; 1995;:651-655.
40 +
Powe NR, Griffiths RI.  The clinical-economic trial: promise, problems, and challenges . Control Clin Trials . 1995;;16:377-394.

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