Обоснование. Антикоагулянты (АК) – препараты высокого риска, неправильное применение которых может приводить к развитию кровотечений и тромбозов. В основе предотвратимых осложнений антикоагулянтной терапии лежат лекарственные ошибки. Выявление и анализ ошибок применения АК позволяет выявить слабые места в системе лекарственной безопасности медицинских организаций. Цель. Разработать эффективный метод систематического выявления ошибок применения АК для последующего изучения, анализа и разработки эффективных мер по повышению безопасности пациентов. Материалы и методы. Исследование проведено в многопрофильном стационаре на 4924 пациентах, госпитализированных в 2019–2021 гг. и получавших АК. По лабораторным триггерам (международное нормализованное отношение ≥4, сывороточный креатинин ≥133 мкмоль/л и скорость клубочковой фильтрации <30 мл/мин/1,73 м2) выявлено 4304 случая. Объединение лабораторных триггеров с данными пациентов, принимающих АК, позволило разработать комбинированные триггеры. Все выявленные по комбинированным триггерам случаи проанализированы двумя клиническими фармакологами, проведена согласованная оценка корректности тактики терапии АК и возможных лекарственных ошибок. Триггер считали положительным при выявлении дефекта применения АК в истории болезни, отобранной по данному триггеру. Результаты. По комбинированным триггерам выявлены 253 пациента с возможными ошибками применения АК (5,3% всех пациентов, принимавших АК). Применение комбинированных триггеров позволило уменьшить количество случаев, подлежащих аудиту, на 97,3%. Ошибки применения выявлены у 137 пациентов. Положительная прогностическая ценность отдельных комбинированных триггеров варьировала от 0 до 63,9%. Совокупная положительная прогностическая ценность используемых в нашем исследовании триггеров составила 54,2%. Дефекты применения АК наблюдались у 2,8% пациентов, которым назначались парентеральные и пероральные АК. Заключение. Представлен метод систематического выявления ошибок применения АК в сплошной выборке госпитализированных пациентов, позволяющий выявить типичные ошибки применения АК для последующего анализа и разработки мер по снижению риска предотвратимого вреда при применении АК.
Ключевые слова: триггеры, ошибки применения лекарственных препаратов, препараты высокого риска, антикоагулянты, неблагоприятные события, нежелательные реакции
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Background. Medication errors can cause preventable adverse events. For example, inappropriate use of anticoagulants (AC) can result in bleeding and thromboembolic complications. Detection and analysis of AC medication errors allow to reveal deficiencies in the safety systems in healthcare organizations. Aim. The study was aimed to develop a method of systematic detection of anticoagulant medication errors for consequent audit, analysis and development of medication safety improvement measures. Materials and methods. The study was conducted in the multidisciplinary hospital and included 4924 patients admitted from January 2019 to December 2021 who received AC. Three laboratory triggers (international normalized ratio ≥4, serum creatinine ≥133 μmol/l, and glomerulofiltration rate <30 ml/min/1.73 m2) helped to reveal 4304 cases. Their matching with patient’s data helped to develop combined triggers. Two clinical pharmacologists reviewed all cases identified by combined triggers for checking medication errors. The trigger was considered positive when anticoagulant medication error was detected in the history selected by combined trigger. Results. Of the 4924 patients 253 (5.3%) were selected by combined triggers. Combined trigger allowed to reduce the amount of medical health records audit by 97.3%. Medication errors were detected in 137 patients. Positive predictive value of selected combined triggers varied from 0 to 63.9%. Aggregated positive predictive value of all combined triggers amounted to 54.2%. AC medication errors were detected in 2.8% patients. Conclusion. Method of systematic detection of AC medication errors using combined triggers in all hospitalized patients receiving AC allowed to reveal typical medication errors for consequent analysis and elaboration of measures to reduce preventable patient harm in healthcare settings.
1. World Health Organization. Patient safety incident reporting and learning systems: technical report and guidance. Geneva: World Health Organization, 2020.
2. Griffin F, Resar RK. IHI Global Trigger Tool for Measuring Adverse Events (Second Edition). IHI Innovation Series white paper. (Available on www.IHI.org). Cambridge, Massachusetts: Institute for Healthcare Improvement, 2009.
3. Pandya AD, Patel K, Rana D, et al. Global Trigger Tool: Proficient Adverse Drug Reaction Autodetection Method in Critical Care Patient Units. Indian J Crit Care Med.
2020;24(3):172-8. DOI:10.5005/jp-journals-10071-23367
4. Hibbert PD, Molloy CJ, Hooper TD, et al. The application of the Global Trigger Tool: a systematic review. Int J Qual Health Care. 2016;28(6):640-9. DOI:10.1093/intqhc/mzw115
5. Classen DC, Resar R, Griffin F, et al. ‘Global Trigger Tool’ Shows That Adverse Events In Hospitals May Be Ten Times Greater Than Previously Measured. Health Affairs.
2011;30(4):581-9. DOI:10.1377/hlthaff.2011.0190
6. Panagioti M, Khan K, Keers RN, et al. Prevalence, severity, and nature of preventable patient harm across medical care settings: systematic review and meta-analysis. BMJ. 2019;l4185. DOI:10.1136/bmj.l4185
7. Walsh EK, Hansen CR, Sahm LJ, et al. Economic impact of medication error: a systematic review: Economic Impact of Medication Error. Pharmacoepidemiol Drug Saf.
2017;26(5):481-97. DOI:10.1002/pds.4188
8. A PINCH – Clinical Excellence Commission. NSW Government. Available at: https://www.cec.health.nsw.gov.au/keep-patients-safe/medication-safety/high-risk-medicines/A-PINCH. Accessed: 11.04.2022.
9. ISMP List of High-Alert Medications in acute care settings. 2018. Available at: https://www.ismp.org/sites/default/files/attachments/2018-08/highAlert2018-Acute-Final.pdf. Accessed: 04.12.2022.
10. Dreijer AR, Diepstraten J, Brouwer R, et al. Risk of bleeding in hospitalized patients on anticoagulant therapy: Prevalence and potential risk factors. Eur J Intern Med. 2019;62:17-23. DOI:10.1016/j.ejim.2019.01.008
11. Mitrovic D, Folkeringa R, Veeger N, et al. Minor bleeding in patients with atrial fibrillation using a non-vitamin-K antagonist oral anticoagulant. Curr Med Res Opin.
2020;36(10):1571-6. DOI:10.1080/03007995.2020.1786808
12. Al Rowily A, Jalal Z, Price MJ, et al. Prevalence, contributory factors and severity of medication errors associated with direct-acting oral anticoagulants in adult patients: a systematic review and meta-analysis. Eur J Clin Pharmacol. 2022;78(4):623-45. DOI:10.1007/s00228-021-03212-y
13. Vinding NE, Butt JH, Olesen JB, et al. Association Between Inappropriately Dosed Anticoagulation Therapy With Stroke Severity and Outcomes in Patients With Atrial Fibrillation. JAHA. 2022;11(6):e024402. DOI:10.1161/JAHA.121.024402
14. Montesi G, Lechi A. Prevention of medication errors: detection and audit. Br J Clin Pharmacol. 2009;67(6):651-5. DOI:10.1111/j.1365-2125.2009.03422.x
15. Rishoej RM, Almarsdóttir AB, Christesen HT, et al. Medication errors in pediatric inpatients: a study based on a national mandatory reporting system. Eur J Pediatr. 2017;176(12):1697-705. DOI:10.1007/s00431-017-3023-8
16. Рекомендации по антитромботической терапии у больных со стабильными проявлениями атеротромбоза. Подготовлены Е.П. Панченко с участием Е.С. Кропачевой. Институт клинической кардиологии им. А.Л. Мясникова. ФГУ РКНПК Росмедтехнологий. Атеротромбоз. 2009;1(2):38-54 [Rekomendatsii po antitromboticheskoi terapii u bolnykh so stabilnymi proyavleniiami aterotromboza. Podgotovleny EP Panchenko s uchastiiem ES Kropachevoi. Institut klinicheskoi kardiologii im. AL Miasnikova. FGU RKNPK Rosmedtekhnologii. Aterotromboz. 2009;1(2):38-54 (in Russian)].
17. Weitz JI, Semchuk W, Turpie AGG, et al. Trends in Prescribing Oral Anticoagulants in Canada, 2008–2014. Clin Therap. 2015;37(11):2506-14.e4. DOI:10.1016/j.clinthera.2015.09.008
18. Kjerpeseth LJ, Ellekjær H, Selmer R, et al. Trends in use of warfarin and direct oral anticoagulants in atrial fibrillation in Norway, 2010 to 2015. Eur J Clin Pharmacol. 2017;73(11):1417-25. DOI:10.1007/s00228-017-2296-1
19. Lutsey PL, Walker RF, MacLehose RF, et al. Direct oral anticoagulants and warfarin for venous thromboembolism treatment: Trends from 2012 to 2017. Res Pract Thromb Haemost. 2019;3(4):668-73. DOI:10.1002/rth2.12222
20. Ho KH, van Hove M, Leng G. Trends in anticoagulant prescribing: a review of local policies in English primary care. BMC Health Serv Res. 2020;20(1):279.
DOI:10.1186/s12913-020-5058-1
21. Brenner S, Detz A, López A, et al. Signal and noise: applying a laboratory trigger tool to identify adverse drug events among primary care patients. BMJ Qual Saf. 2012;21(8):670-5. DOI:10.1136/bmjqs-2011-000643
22. Buckley MS, Rasmussen JR, Bikin DS, et al. Trigger alerts associated with laboratory abnormalities on identifying potentially preventable adverse drug events in the intensive care unit and general ward. Therap Adv Drug Saf. 2018;9(4):207-17. DOI:10.1177/2042098618760995
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1. World Health Organization. Patient safety incident reporting and learning systems: technical report and guidance. Geneva: World Health Organization, 2020.
2. Griffin F, Resar RK. IHI Global Trigger Tool for Measuring Adverse Events (Second Edition). IHI Innovation Series white paper. (Available on www.IHI.org). Cambridge, Massachusetts: Institute for Healthcare Improvement, 2009.
3. Pandya AD, Patel K, Rana D, et al. Global Trigger Tool: Proficient Adverse Drug Reaction Autodetection Method in Critical Care Patient Units. Indian J Crit Care Med.
2020;24(3):172-8. DOI:10.5005/jp-journals-10071-23367
4. Hibbert PD, Molloy CJ, Hooper TD, et al. The application of the Global Trigger Tool: a systematic review. Int J Qual Health Care. 2016;28(6):640-9. DOI:10.1093/intqhc/mzw115
5. Classen DC, Resar R, Griffin F, et al. ‘Global Trigger Tool’ Shows That Adverse Events In Hospitals May Be Ten Times Greater Than Previously Measured. Health Affairs.
2011;30(4):581-9. DOI:10.1377/hlthaff.2011.0190
6. Panagioti M, Khan K, Keers RN, et al. Prevalence, severity, and nature of preventable patient harm across medical care settings: systematic review and meta-analysis. BMJ. 2019;l4185. DOI:10.1136/bmj.l4185
7. Walsh EK, Hansen CR, Sahm LJ, et al. Economic impact of medication error: a systematic review: Economic Impact of Medication Error. Pharmacoepidemiol Drug Saf.
2017;26(5):481-97. DOI:10.1002/pds.4188
8. A PINCH – Clinical Excellence Commission. NSW Government. Available at: https://www.cec.health.nsw.gov.au/keep-patients-safe/medication-safety/high-risk-medicines/A-PINCH. Accessed: 11.04.2022.
9. ISMP List of High-Alert Medications in acute care settings. 2018. Available at: https://www.ismp.org/sites/default/files/attachments/2018-08/highAlert2018-Acute-Final.pdf. Accessed: 04.12.2022.
10. Dreijer AR, Diepstraten J, Brouwer R, et al. Risk of bleeding in hospitalized patients on anticoagulant therapy: Prevalence and potential risk factors. Eur J Intern Med. 2019;62:17-23. DOI:10.1016/j.ejim.2019.01.008
11. Mitrovic D, Folkeringa R, Veeger N, et al. Minor bleeding in patients with atrial fibrillation using a non-vitamin-K antagonist oral anticoagulant. Curr Med Res Opin.
2020;36(10):1571-6. DOI:10.1080/03007995.2020.1786808
12. Al Rowily A, Jalal Z, Price MJ, et al. Prevalence, contributory factors and severity of medication errors associated with direct-acting oral anticoagulants in adult patients: a systematic review and meta-analysis. Eur J Clin Pharmacol. 2022;78(4):623-45. DOI:10.1007/s00228-021-03212-y
13. Vinding NE, Butt JH, Olesen JB, et al. Association Between Inappropriately Dosed Anticoagulation Therapy With Stroke Severity and Outcomes in Patients With Atrial Fibrillation. JAHA. 2022;11(6):e024402. DOI:10.1161/JAHA.121.024402
14. Montesi G, Lechi A. Prevention of medication errors: detection and audit. Br J Clin Pharmacol. 2009;67(6):651-5. DOI:10.1111/j.1365-2125.2009.03422.x
15. Rishoej RM, Almarsdóttir AB, Christesen HT, et al. Medication errors in pediatric inpatients: a study based on a national mandatory reporting system. Eur J Pediatr. 2017;176(12):1697-705. DOI:10.1007/s00431-017-3023-8
16. Rekomendatsii po antitromboticheskoi terapii u bolnykh so stabilnymi proyavleniiami aterotromboza. Podgotovleny EP Panchenko s uchastiiem ES Kropachevoi. Institut klinicheskoi kardiologii im. AL Miasnikova. FGU RKNPK Rosmedtekhnologii. Aterotromboz. 2009;1(2):38-54 (in Russian).
17. Weitz JI, Semchuk W, Turpie AGG, et al. Trends in Prescribing Oral Anticoagulants in Canada, 2008–2014. Clin Therap. 2015;37(11):2506-14.e4. DOI:10.1016/j.clinthera.2015.09.008
18. Kjerpeseth LJ, Ellekjær H, Selmer R, et al. Trends in use of warfarin and direct oral anticoagulants in atrial fibrillation in Norway, 2010 to 2015. Eur J Clin Pharmacol. 2017;73(11):1417-25. DOI:10.1007/s00228-017-2296-1
19. Lutsey PL, Walker RF, MacLehose RF, et al. Direct oral anticoagulants and warfarin for venous thromboembolism treatment: Trends from 2012 to 2017. Res Pract Thromb Haemost. 2019;3(4):668-73. DOI:10.1002/rth2.12222
20. Ho KH, van Hove M, Leng G. Trends in anticoagulant prescribing: a review of local policies in English primary care. BMC Health Serv Res. 2020;20(1):279.
DOI:10.1186/s12913-020-5058-1
21. Brenner S, Detz A, López A, et al. Signal and noise: applying a laboratory trigger tool to identify adverse drug events among primary care patients. BMJ Qual Saf. 2012;21(8):670-5. DOI:10.1136/bmjqs-2011-000643
22. Buckley MS, Rasmussen JR, Bikin DS, et al. Trigger alerts associated with laboratory abnormalities on identifying potentially preventable adverse drug events in the intensive care unit and general ward. Therap Adv Drug Saf. 2018;9(4):207-17. DOI:10.1177/2042098618760995
1ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Москва, Россия; 2ФГБУ «Национальный медицинский исследовательский центр травматологии и ортопедии им. Н.Н. Приорова», Москва, Россия; 3Многопрофильный медицинский центр Центрального банка Российской Федерации, Москва, Россия; 4ГБУЗ «Городская клиническая больница №52» Департамента здравоохранения г. Москвы, Москва, Россия
*vitotd@yandex.ru
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Vitaly A. Otdelenov*1,2, Elena B. Kleymenova1,2, Maria D. Nigmatkulova3, Svetlana A. Payushchik2, Olga D. Dukhanina1,4, Liubov P. Yashina2, Dmitry A. Sychev1
1Russian Medical Academy of Continuous Professional Education, Moscow, Russia; 2Priorov National Medical Research Center for Traumatology and Orthopedics, Moscow, Russia; 3General Medical Center of the Central Bank of Russia, Moscow, Russia; 4Sity Clinical Hospital №52, Moscow, Russia
*vitotd@yandex.ru