항콜린약물부담이 한국 노인의 응급실 방문에 미치는 영향

Abstract

항콜린약물의 사용은 입마름, 변비, 뇨저류, 어지러움, 섬망, 치매 등에 이르는 다양한 부작용을 일으킬 수 있다. 특히 노인들은 노화에 따른 신체적 변화로 인해 이러한 부작용에 취약해, 항콜린약물은 노인들은 가능한 피해야 할 노인주의약물 중 하나이다. 다양한 항콜린약물부담 평가 도구들은 여러 항콜린약물을 사용하는데 따른 누적적인 항콜린약물의 노출 정도(“항콜린약물부담”)를 측정하기 위해 개발되어 왔다. 한국형 항콜린약물부담 평가 도구(Korean Anticholinergic Burden Scale, KABS)는 한국의 약물사용현황을 반영하기 위해, 문헌고찰과 델파이 기법을 이용한 전문가 합의를 통해 개발되었다. 본 연구는 2016년 건강보험심사평가원의 노인표본자료를 이용하여, 두 가지 연구를 진행하였다. 첫 번째 코호트 연구에서는 높은 항콜린약물부담이 응급실 방문과 항콜린 부작용으로 인한 응급실 방문에 미치는 영향을 평가하였고, 두 번째 코호트 내 환자-대조군 연구에서는 새로 개발된 한국형 항콜린약물부담 평가 도구를 이전에 해외에서 개발되어 검증된 도구들과 비교하여 그 유효성을 검증하고자 하였다.

Part Ⅰ 높은 항콜린약물부담이 한국 노인의 응급실 방문에 미치는 영향

첫 번째 후향적 코호트 연구는 4월부터 6월까지 3개월 동안의 일평균 Anticholinergic Risk Scale (ARS) 점수가 2점 이상인 높은 항콜린약물부담을 가진 노인환자와 항콜린약물을 전혀 복용하지 않는 노인환자로 코호트를 구성하여, 이후 7월부터 9월까지 3개월 동안의 추적관찰 기간 동안 응급실 방문을 살펴보았다. 연령, 성별, 보험유형, 병존 질환, 병용약물을 고려한 다변량 회귀분석 결과에서, 높은 항콜린약물부담을 가진 노인환자는 응급실 방문할 위험이 1.28배(95% CI: 1.20–1.36) 높았으며, 낙상 및 골절, 어지러움, 섬망, 변비나 뇨저류 등 항콜린 부작용으로 응급실을 방문할 위험은 1.55배(95% CI: 1.38–1.74) 높았다. 또한 개별 항콜린 부작용으로 인한 응급실 방문 위험과 관련해서는 낙상이나 골절은 1.31배(95% CI: 1.07–1.60), 어지러움은 1.71배(95% CI: 1.36–2.14), 섬망은 2.05배(95% CI: 1.13–3.73), 변비는 1.65배(95% CI: 1.35–2.02), 뇨저류의 경우 1.66배(95% CI: 1.30–2.12)로 위험이 증가하는 것으로 나타났다.

Part Ⅱ 한국형 항콜린약물부담 평가 도구의 임상적 유효성 검증

본 연구에서는 2016년 7월 한 달 동안 응급실을 방문한 노인을 환자군으로 응급실을 방문하지 않는 노인을 대조군으로 하여, 응급실 방문 관찰 이전 6월 한 달 동안의 항콜린약물부담을 KABS, ARS, Anticholinergic Cognitive Burden (ACB), Anticholinergic Drug Scale (ADS)를 이용하여 평가하였다. 전체 1,284,975명의 노인환자에서 항콜린약물을 복용하는 노인환자의 비율은 36.4%에서 56.0%로 사용한 항콜린약물부담 평가 도구 별로 다르게 나타났다. 다른 도구들과 마찬가지로 KABS는 응급실 방문, 응급 입원, 항콜린 부작용으로 인한 응급실 방문과 용량 의존적인 오즈비 증가를 보였다. 그러나 KABS는 항콜린 부작용으로 인한 응급실방문과 관련하여 다른 도구들에 비해 상대적으로 높은 상관성을 보여주었고, 개별 항콜린 부작용으로 인한 응급실 방문과의 상관성에서는 다른 도구들과 달리, 유일하게 KABS만 용량 의존적 관계를 일관성 있게 보여주었다.

두 연구를 통해, 높은 항콜린약물부담은 응급실 방문의 위험을 높이는 것으로 나타났으며, 한국형 항콜린약물부담 평가 도구는 응급실 방문을 초래하는 다양한 항콜린 부작용과의 일관된 상관성을 보여줌을 통해 그 유효성을 검증하였다. 따라서 한국형 항콜린약물부담 평가 도구는 불필요한 항콜린약물 사용을 줄이는데 유용한 도구로 활용될 수 있을 것으로 보인다.|Background It is widely recognized that the use of medications with anticholinergic properties can cause a variety of adverse effects, including dry mouth, constipation, urinary retention, dizziness, delirium, and severe cognitive decline. Older adults are especially vulnerable to these harmful effects due to physiologic age-related changes, so that anticholinergics are often involved in explicit criteria for potentially inappropriate prescribing in older adults. Numerous anticholinergic burden scales have been developed to quantify the cumulative anticholinergic exposure of using multiple medications, defined as “anticholinergic burden (AB)”. To reflect the availability of the medications in Korea, the Korean Anticholinergic Burden Scale (KABS) was developed using the Delphi methods after reviewing previous scales.

Part Ⅰ: Impact of high anticholinergic burden on emergency department visits among older adults in Korea: A national population cohort study Objectives: This study aimed to evaluate the impact of high anticholinergic burden on overall emergency department (ED) visits and ED visits related to adverse effects of anticholinergic drugs among older adults. Methods: For this retrospective cohort study, we used claims data from older adults with high representativeness. The average daily Anticholinergic Risk Scale (ARS) score was calculated based on the dosage, treatment duration, and potency of anticholinergic drugs during three months. A high-exposure group (ARS≥2) and a non-exposure group were included in this analysis. The primary outcome was the first ED visit during the follow-up period. Anticholinergic ED visits were defined as ED visits with a main diagnosis of a fall, fracture, dizziness, delirium, constipation, or urinary retention. Results: In total, 118,750 subjects (43.6% male) were included in this study. The mean age was 75.4 ± 6.6 years. The adjusted hazard ratios (aHRs) for all-cause and anticholinergic ED visits among those with high ARS scores were 1.28 (95% CI: 1.20–1.36) and 1.55 (95% CI: 1.38–1.74), respectively. The high-exposure group was at higher risk than the non-exposure group for ED visits for falls or fractures (aHR: 1.31, 95% CI: 1.07–1.60), dizziness (aHR: 1.71, 95% CI: 1.36–2.14), delirium (aHR: 2.05, 95% CI: 1.13–3.73), constipation (aHR: 1.65, 95% CI: 1.35–2.02) and urinary retention (aHR: 1.66, 95% CI: 1.30–2.12).

Part Ⅱ: Validation study of the Korean Anticholinergic Burden Scale compared to other scales: A nested case-control study Objectives: The aim of the current study was to investigate the validity of the KABS by evaluating correlations between AB measured via the KABS and ED visits compared to other scales. Methods: This nested case-control study used an adult patient sample dataset provided by the Health Insurance Review and Assessment Service in 2016. The average daily AB score for the month of June was measured considering the dosage, treatment duration, and anticholinergic potency of drugs listed in the KABS in comparison with the Anticholinergic Risk Scale (ARS), Anticholinergic Cognitive Burden (ACB), and Anticholinergic Drug Scale (ADS). Multivariate logistic regression analysis was used to investigate relationships between ED visits in July and AB, incorporating adjustments for age, sex, co-morbid disease, co-medications (sedative drugs, insulin, digoxin, and warfarin), and prior ED visits. Results: A total of 1,284,975 subjects (41.7% male) were included in the present analysis, and their mean age was 73.8 ± 6.6 years. Prevalence of exposure to anticholinergics ranged from 36.4% to 56.0% depending on which scale was used. In multivariate regression analysis there were dose-dependent associations between AB as measured by the KABS and all-cause ED visits, emergency hospitalizations, and anticholinergic ED visits. Results derived from the KABS were relatively highly correlated with anticholinergic adverse effects as determined via the ARS, ACB, and ADS, which have already been validated. The KABS only exhibited a consistent correlation with negative outcomes that included individual anticholinergic adverse events.

Conclusions Part Ⅰ of the present study demonstrated that a high anticholinergic burden in older adults increased the risk of all-cause ED visits and anticholinergic ED visits. In Part Ⅱ, the KABS was validated in that there were dose-dependent relationships between various adverse outcomes and AB quantified by the KABS. These results highlight a need to increase the awareness, identification, and resolution of these medication-related problems contributing to unintended drug-related ED visits. The KABS may be a practical tool for assessing AB in Korean older adults in routine medication reviews and in medical studies.; Background It is widely recognized that the use of medications with anticholinergic properties can cause a variety of adverse effects, including dry mouth, constipation, urinary retention, dizziness, delirium, and severe cognitive decline. Older adults are especially vulnerable to these harmful effects due to physiologic age-related changes, so that anticholinergics are often involved in explicit criteria for potentially inappropriate prescribing in older adults. Numerous anticholinergic burden scales have been developed to quantify the cumulative anticholinergic exposure of using multiple medications, defined as “anticholinergic burden (AB)”. To reflect the availability of the medications in Korea, the Korean Anticholinergic Burden Scale (KABS) was developed using the Delphi methods after reviewing previous scales.

Part Ⅰ: Impact of high anticholinergic burden on emergency department visits among older adults in Korea: A national population cohort study Objectives: This study aimed to evaluate the impact of high anticholinergic burden on overall emergency department (ED) visits and ED visits related to adverse effects of anticholinergic drugs among older adults. Methods: For this retrospective cohort study, we used claims data from older adults with high representativeness. The average daily Anticholinergic Risk Scale (ARS) score was calculated based on the dosage, treatment duration, and potency of anticholinergic drugs during three months. A high-exposure group (ARS≥2) and a non-exposure group were included in this analysis. The primary outcome was the first ED visit during the follow-up period. Anticholinergic ED visits were defined as ED visits with a main diagnosis of a fall, fracture, dizziness, delirium, constipation, or urinary retention. Results: In total, 118,750 subjects (43.6% male) were included in this study. The mean age was 75.4 ± 6.6 years. The adjusted hazard ratios (aHRs) for all-cause and anticholinergic ED visits among those with high ARS scores were 1.28 (95% CI: 1.20–1.36) and 1.55 (95% CI: 1.38–1.74), respectively. The high-exposure group was at higher risk than the non-exposure group for ED visits for falls or fractures (aHR: 1.31, 95% CI: 1.07–1.60), dizziness (aHR: 1.71, 95% CI: 1.36–2.14), delirium (aHR: 2.05, 95% CI: 1.13–3.73), constipation (aHR: 1.65, 95% CI: 1.35–2.02) and urinary retention (aHR: 1.66, 95% CI: 1.30–2.12).

Part Ⅱ: Validation study of the Korean Anticholinergic Burden Scale compared to other scales: A nested case-control study Objectives: The aim of the current study was to investigate the validity of the KABS by evaluating correlations between AB measured via the KABS and ED visits compared to other scales. Methods: This nested case-control study used an adult patient sample dataset provided by the Health Insurance Review and Assessment Service in 2016. The average daily AB score for the month of June was measured considering the dosage, treatment duration, and anticholinergic potency of drugs listed in the KABS in comparison with the Anticholinergic Risk Scale (ARS), Anticholinergic Cognitive Burden (ACB), and Anticholinergic Drug Scale (ADS). Multivariate logistic regression analysis was used to investigate relationships between ED visits in July and AB, incorporating adjustments for age, sex, co-morbid disease, co-medications (sedative drugs, insulin, digoxin, and warfarin), and prior ED visits. Results: A total of 1,284,975 subjects (41.7% male) were included in the present analysis, and their mean age was 73.8 ± 6.6 years. Prevalence of exposure to anticholinergics ranged from 36.4% to 56.0% depending on which scale was used. In multivariate regression analysis there were dose-dependent associations between AB as measured by the KABS and all-cause ED visits, emergency hospitalizations, and anticholinergic ED visits. Results derived from the KABS were relatively highly correlated with anticholinergic adverse effects as determined via the ARS, ACB, and ADS, which have already been validated. The KABS only exhibited a consistent correlation with negative outcomes that included individual anticholinergic adverse events.

Conclusions Part Ⅰ of the present study demonstrated that a high anticholinergic burden in older adults increased the risk of all-cause ED visits and anticholinergic ED visits. In Part Ⅱ, the KABS was validated in that there were dose-dependent relationships between various adverse outcomes and AB quantified by the KABS. These results highlight a need to increase the awareness, identification, and resolution of these medication-related problems contributing to unintended drug-related ED visits. The KABS may be a practical tool for assessing AB in Korean older adults in routine medication reviews and in medical studies.