Skip to main content
Top
Published in: Intensive Care Medicine 12/2007

01-12-2007 | Original

Life-threatening adverse drug reactions at admission to medical intensive care: a prospective study in a teaching hospital

Authors: Marieke Grenouillet-Delacre, Hélène Verdoux, Nicholas Moore, Françoise Haramburu, Ghada Miremont-Salamé, Gabriel Etienne, Philip Robinson, Didier Gruson, Gilles Hilbert, Claude Gabinski, Bernard Bégaud, Mathieu Molimard

Published in: Intensive Care Medicine | Issue 12/2007

Login to get access

Abstract

Objective

To assess the characteristics of life-threatening adverse drug reactions in patients admitted to medical intensive care unit and to define those that could facilitate early identification.

Design

A prospective 6-month observational study.

Patients

Of the 436 admissions to the teaching hospital medical intensive care unit, all patients aged over 15 years and who had received documented drug treatment were included (n = 405).

Measurements

Characteristics of patients [age, gender, underlying diseases, organ failure(s), drugs taken, Severity Acute Physiologic Score II, length of stay, outcome at discharge] were prospectively collected using a standardised questionnaire. A panel of experts assessed putative serious adverse drug reaction(s) for each drug taken and each organ failure at admission by using a standardised causality assessment method. Characteristics of patients with and without serious adverse drug reactions at admission were compared using univariate and then stepwise descending multivariate logistic regression.

Results

Of the 405 patients included, 111 (27.4%) presented an adverse drug reaction leading to organ failure. In 48% of cases adverse drug reactions were preventable, 23% were undiagnosed and 19% contributed to death. Age over 75 years [odds ratio (OR) 2.25; 95% confidence interval (CI) 1.15–4.38; p = 0.02], having more than three drugs (OR 6.90; 95% CI 1.44–33.00; p = 0.02) and a diagnosis of haematological malignancy (OR 6.19; 95% CI 2.07–18.53; p = 0.001) were independently associated with serious adverse drug reactions.

Conclusions

Preventable life-threatening adverse drug reactions were frequently involved in organ failure at admission to medical intensive care; many of them had not been identified.
Literature
1.
go back to reference Bates DW, Cullen DJ, Laird N, Petersen LA, Small SD, Servi D, Laffel G, Sweitzer BJ, Shea BF, Hallisey R, for the Adverse Drug Event Prevention Study Group (1995) Incidence of adverse drug events and potential adverse drug events: implications for prevention. JAMA 274:29–34PubMedCrossRef Bates DW, Cullen DJ, Laird N, Petersen LA, Small SD, Servi D, Laffel G, Sweitzer BJ, Shea BF, Hallisey R, for the Adverse Drug Event Prevention Study Group (1995) Incidence of adverse drug events and potential adverse drug events: implications for prevention. JAMA 274:29–34PubMedCrossRef
2.
go back to reference Moore N, Lecointre D, Noblet C, Mabille M (1998) Frequency and cost of serious adverse drug reactions in a department of general medicine. Br J Clin Pharmacol 45:301–308PubMedCrossRef Moore N, Lecointre D, Noblet C, Mabille M (1998) Frequency and cost of serious adverse drug reactions in a department of general medicine. Br J Clin Pharmacol 45:301–308PubMedCrossRef
3.
go back to reference Juntti-Pattinen L, Neuvonen PJ (2002) Drug-related deaths in a university central hospital. Eur J Clin Pharmacol 58:479–482CrossRef Juntti-Pattinen L, Neuvonen PJ (2002) Drug-related deaths in a university central hospital. Eur J Clin Pharmacol 58:479–482CrossRef
4.
go back to reference Hayward RA, Hofer TP (2001) Estimating hospital deaths due to medical errors: preventability is in the eye of the reviewer. JAMA 286:415–420PubMedCrossRef Hayward RA, Hofer TP (2001) Estimating hospital deaths due to medical errors: preventability is in the eye of the reviewer. JAMA 286:415–420PubMedCrossRef
5.
go back to reference Trunet P, Le Gall JR, Lhoste F, Regnier B, Saillard Y, Carlet J, Rapin M (1980) The role of iatrogenic disease in admissions to intensive care. JAMA 244:2617–2620PubMedCrossRef Trunet P, Le Gall JR, Lhoste F, Regnier B, Saillard Y, Carlet J, Rapin M (1980) The role of iatrogenic disease in admissions to intensive care. JAMA 244:2617–2620PubMedCrossRef
6.
go back to reference Farina ML, Tognoni G, Procaccio F, Italian Group on Intensive Care Evaluation (1987) Epidemiology of adverse drug reactions in intensive care units. A multicentre prospective survey. Eur J Clin Pharmacol 31:507–512CrossRef Farina ML, Tognoni G, Procaccio F, Italian Group on Intensive Care Evaluation (1987) Epidemiology of adverse drug reactions in intensive care units. A multicentre prospective survey. Eur J Clin Pharmacol 31:507–512CrossRef
7.
go back to reference Darchy B, Le Mière E, Figuérédo B, Bavoux E, Domart Y (1999) Iatrogenic diseases as a reason for admission to the intensive care unit. Arch Intern Med 159:71–78PubMedCrossRef Darchy B, Le Mière E, Figuérédo B, Bavoux E, Domart Y (1999) Iatrogenic diseases as a reason for admission to the intensive care unit. Arch Intern Med 159:71–78PubMedCrossRef
9.
go back to reference Bégaud B, Evreux JC, Jouglard J, Lagier G (1985) Imputation of the unexpected or toxic effects of drugs. Actualization of the method used in France. Therapie 40:111–118PubMed Bégaud B, Evreux JC, Jouglard J, Lagier G (1985) Imputation of the unexpected or toxic effects of drugs. Actualization of the method used in France. Therapie 40:111–118PubMed
10.
go back to reference Martin K, Bégaud B, Latry P, Miremont-Salamé G, Fourrier A, Moore N (2003) Differences between clinical trials and postmarketing use. Br J Clin Pharmacol 57:86–92CrossRef Martin K, Bégaud B, Latry P, Miremont-Salamé G, Fourrier A, Moore N (2003) Differences between clinical trials and postmarketing use. Br J Clin Pharmacol 57:86–92CrossRef
13.
go back to reference Nebeker JR, Barach P, Samore MH (2004) Clarifying adverse drug events: A clinician's guide to terminology, documentation and reporting. Ann Intern Med 140:795–801PubMed Nebeker JR, Barach P, Samore MH (2004) Clarifying adverse drug events: A clinician's guide to terminology, documentation and reporting. Ann Intern Med 140:795–801PubMed
14.
go back to reference Cullen DJ, Sweitzer BJ, Bates DW, Burdick E, Edmondson A, Leape LL (1997) Preventable adverse drug events in hospitalized patients: a comparative study of intensive care and general care units. Crit Care Med 25:1289–1297PubMedCrossRef Cullen DJ, Sweitzer BJ, Bates DW, Burdick E, Edmondson A, Leape LL (1997) Preventable adverse drug events in hospitalized patients: a comparative study of intensive care and general care units. Crit Care Med 25:1289–1297PubMedCrossRef
15.
go back to reference Dictionnaire Vidal® (2003) Editions Vidal, France Dictionnaire Vidal® (2003) Editions Vidal, France
16.
go back to reference Lindquist M, Edwards IR (2001) The WHO programme for International Drug Monitoring, its database, and the technical support of the Upssala Monitoring Center. J Rheumatol 28:1180–1187PubMed Lindquist M, Edwards IR (2001) The WHO programme for International Drug Monitoring, its database, and the technical support of the Upssala Monitoring Center. J Rheumatol 28:1180–1187PubMed
17.
go back to reference Corso DM, Pucino F, DeLeo JM, Gallelli JF (1992) Development of a questionnaire for detecting potential adverse drug reactions. Ann Pharmacother 26:890–896PubMed Corso DM, Pucino F, DeLeo JM, Gallelli JF (1992) Development of a questionnaire for detecting potential adverse drug reactions. Ann Pharmacother 26:890–896PubMed
19.
go back to reference Schneeweiss S, Gottler M, Hasford J, Swoboda W, Hippius M, Hoffmann AK, Riethling AK, Krappweis J (2001) First results from an intensified monitoring system to estimate drug related hospital admissions. Br J Clin Pharmacol 52:196–200PubMedCrossRef Schneeweiss S, Gottler M, Hasford J, Swoboda W, Hippius M, Hoffmann AK, Riethling AK, Krappweis J (2001) First results from an intensified monitoring system to estimate drug related hospital admissions. Br J Clin Pharmacol 52:196–200PubMedCrossRef
20.
go back to reference Haynes BF, Fauci AS (2000) Cellular and molecular immunology. In: Harrison's principles of internal medicine. McGraw Hill International, London, pp 2018–2023 Haynes BF, Fauci AS (2000) Cellular and molecular immunology. In: Harrison's principles of internal medicine. McGraw Hill International, London, pp 2018–2023
21.
go back to reference Task Force of the American College of Critical Care Medicine. Society of Critical Care Medicine (1999) Guidelines for intensive care unit admission, discharge, and triage. Crit Care Med 27:633–638CrossRef Task Force of the American College of Critical Care Medicine. Society of Critical Care Medicine (1999) Guidelines for intensive care unit admission, discharge, and triage. Crit Care Med 27:633–638CrossRef
22.
go back to reference Lemeshow S, Le Gall JR (1994) Modeling the severity of illness of ICU patients: a systems update. JAMA 272:1049–1055PubMedCrossRef Lemeshow S, Le Gall JR (1994) Modeling the severity of illness of ICU patients: a systems update. JAMA 272:1049–1055PubMedCrossRef
23.
25.
go back to reference Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberst EA, Janecek E, Domecq C, Greenblatt DJ (1981) A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 30:239–245PubMedCrossRef Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberst EA, Janecek E, Domecq C, Greenblatt DJ (1981) A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 30:239–245PubMedCrossRef
26.
go back to reference Auriche M, Loupi E (1993) Does proof of causality exist in pharmacovigilance? Drug Safety 9:230–235PubMed Auriche M, Loupi E (1993) Does proof of causality exist in pharmacovigilance? Drug Safety 9:230–235PubMed
27.
go back to reference Arimone Y, Bégaud B, Miremont-Salamé G, Fourrier-Réglat A, Moore N, Molimard M, Haramburu F (2005) Agreement of expert judgment in causality assessment of adverse drug reactions. Eur J Clin Pharm 61:169–173CrossRef Arimone Y, Bégaud B, Miremont-Salamé G, Fourrier-Réglat A, Moore N, Molimard M, Haramburu F (2005) Agreement of expert judgment in causality assessment of adverse drug reactions. Eur J Clin Pharm 61:169–173CrossRef
28.
go back to reference Hosmer DW, Lemeshow S (2000) Applied logistic regression. Wiley, New York Hosmer DW, Lemeshow S (2000) Applied logistic regression. Wiley, New York
29.
go back to reference Michel P, Quenon JL, de Sarasqueta AM, Scemama O (2004) Comparison of three methods for estimating rates of adverse events and rates of preventable events in acute care hospitals. Br Med J 328:199–202CrossRef Michel P, Quenon JL, de Sarasqueta AM, Scemama O (2004) Comparison of three methods for estimating rates of adverse events and rates of preventable events in acute care hospitals. Br Med J 328:199–202CrossRef
30.
go back to reference Johnson JA, Lyle Bootman J (1995) Drug-related morbidity and mortality. Arch Intern Med 155:1949–1956PubMedCrossRef Johnson JA, Lyle Bootman J (1995) Drug-related morbidity and mortality. Arch Intern Med 155:1949–1956PubMedCrossRef
31.
go back to reference Azoulay E, Recher C, Alberti C, Soufir L, Leleu G, Le Gall JR, Fernand JP, Schlemmer B (1999) Changing use of intensive care in hematological patients: the example of multiple myeloma. Intensive Care Med 25:1395–1401PubMedCrossRef Azoulay E, Recher C, Alberti C, Soufir L, Leleu G, Le Gall JR, Fernand JP, Schlemmer B (1999) Changing use of intensive care in hematological patients: the example of multiple myeloma. Intensive Care Med 25:1395–1401PubMedCrossRef
32.
go back to reference Zanotti KM, Markman M (2001) Prevention and management of antineoplastics-induced hypersensitivity reactions. Drug Safety 24:767–779PubMedCrossRef Zanotti KM, Markman M (2001) Prevention and management of antineoplastics-induced hypersensitivity reactions. Drug Safety 24:767–779PubMedCrossRef
33.
go back to reference Lapeyre-Mestre M, Gary J, Machelard-Roumagnac M, Bonhomme C, Bugat R, Montastruc JL (1997) Incidence and cost of adverse drug reactions in a French cancer institute. Eur J Clin Pharmacol 53:19–22PubMedCrossRef Lapeyre-Mestre M, Gary J, Machelard-Roumagnac M, Bonhomme C, Bugat R, Montastruc JL (1997) Incidence and cost of adverse drug reactions in a French cancer institute. Eur J Clin Pharmacol 53:19–22PubMedCrossRef
34.
go back to reference Bates DW, Miller EB, Cullen DJ, Burdick L, Williams L, Laird N, Petersen LA, Small SD, Sweitzer BJ, Vander Vliet M, Leape LL, for the Adverse Drug Event Prevention Study Group (1999) Patient risk factors for adverse drugs events in hospitalized patients. ADE Prevention Study Group. Arch Int Med 159:2553–2560CrossRef Bates DW, Miller EB, Cullen DJ, Burdick L, Williams L, Laird N, Petersen LA, Small SD, Sweitzer BJ, Vander Vliet M, Leape LL, for the Adverse Drug Event Prevention Study Group (1999) Patient risk factors for adverse drugs events in hospitalized patients. ADE Prevention Study Group. Arch Int Med 159:2553–2560CrossRef
35.
go back to reference Begaud B, Martin K, Fourrier A, Haramburu F (2002) Does age increase the risk of adverse reactions? Br J Clin Pharmacol 54:550–552PubMedCrossRef Begaud B, Martin K, Fourrier A, Haramburu F (2002) Does age increase the risk of adverse reactions? Br J Clin Pharmacol 54:550–552PubMedCrossRef
Metadata
Title
Life-threatening adverse drug reactions at admission to medical intensive care: a prospective study in a teaching hospital
Authors
Marieke Grenouillet-Delacre
Hélène Verdoux
Nicholas Moore
Françoise Haramburu
Ghada Miremont-Salamé
Gabriel Etienne
Philip Robinson
Didier Gruson
Gilles Hilbert
Claude Gabinski
Bernard Bégaud
Mathieu Molimard
Publication date
01-12-2007
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 12/2007
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-007-0787-8

Other articles of this Issue 12/2007

Intensive Care Medicine 12/2007 Go to the issue