고령 남성 환자에서의 opioid 유해반응 발현 위험 인자 연구

Abstract

연구 배경: 지난 수십 년간 통증 조절을 위한 opioid 사용은 급격히 증가하고 있고, 이의 효과와 더불어 유해반응 보고도 증가하고 있다. 특히, 고령의 환자는 여러 기저 질환으로 인한 다 약제 복용으로 약물 상호작용의 가능성이 높아 opioid 처방에 주의가 필요하다. 이에 고령 환자에서의 opioid 유해반응 발현율 및 양상을 확인하고, 관련 인자를 파악해 보고자 한다. 연구 방법: 2012년 1월 1일부터 2012년 12월 31일까지 중앙보훈병원 외래에서 경구용 opioid (codeine phosphate, fentanyl citrate, morphine sulfate, oxycodone HCl, pentazocin)를 원내 투약 받은 65세 이상의 남성 환자의 전자 의무기록을 후향적으로 검토하였다. 이를 유해반응 발현군과 비발현군으로 나누어 연령, 체질량지수, 음주 및 흡연여부, 기저질환, 이전 opioid 사용 경험, 병용약물 등과의 상관관계를 분석하였다. 연구 결과: 총 320명의 대상 환자 중 89명(27.8%)의 환자에서 유해반응이 발현되었고, 발현 양상은 변비 36명(11.3%), 위장장애 27명(8.4%), 오심, 구토 24명(7.5%), 어지러움 12명(3.8%), 졸음, 정신착란 8명(2.5%), 배뇨장애 7명(2.2%), 피부 유해반응 5명(1.6%), 호흡 유해반응 2명(0.6%), 기타 31명(9.7%)로 나타났다. 유해반응 발현 관련인자에 대해 opioid 종류와 opioid 병용의 변수를 각각 따로 포함하는 두 가지 Model로 다변량 분석을 시행한 결과 opioid 종류에 있어서는 암(OR=0.305, 95% CI=0.145-0.642), 90일 이상의 처방기간(OR=2.127, 95% CI=1.137-3.980)이 의미 있는 변수로 나타났고, codeine에 비해 morphine이 약 7.5배(95% CI=2.547-22.208), oxycodone이 약 7.3배(95% CI= 2.545-20.701) 더 유해반응이 나타났다. opioid 병용에 있어서는 암(OR=0.323, 95% CI= 0.169-0.617), 90일 이상의 처방기간(OR=2.054, 95% CI=1.149-3.673), GABA analogue 병용(OR=3.259, 95% CI=1.777-5.977)이 의미 있는 변수로 나타났고, 단일 opioid 사용에 비해 두 종 류 이상의 opioid 병용 시 약 2.8배(95% CI=1.089-7.163) 더 유해반응이 많이 나타났다. 결론: 고령 남성 환자의 opioid 복용에 있어 상대적으로 유해반응 발현을 낮추는 관련 인자로는 암과 opioid 종류로 codeine이, 유해반응 발현을 상승시키는 관련 인자로는 장기간의 처방, GABA analogue 병용과 두 종류 이상의 opioid 병용으로 나왔다. 본 연구는 후향적 연구로써 한계점이 있으므로 향후 본 연구에서 다루지 못한 관련 인자를 포함한 추가적 연구가 필요한 바이다.;Background Opioid administration for pain control has rapidly increased in the last several decades, and reports of adverse reactions associated with opioid application have also skyrocketed. In particular, elderly patients with various underlying disorders are administered with multiple drugs and prone to drug-drug interactions, and special attention is necessary in prescribing opioids. Thus, this study attempts to verify the incidence rates of opioid adverse reactions and their manifestations, and to examine relevant causative factors in elderly male patients. Method This retrospective study, conducted via electronic medical records, included a total of 320 male patients with an age of 65 years or older who had been prescribed with oral opioid drug(s) (such as codeine phosphate, fentanyl citrate, morphine sulfate, oxycodone HCL, or pentazocin) at the outpatient department of this hospital from January 1 to December 31 in 2012. These subjects were divided into two groups: Group one for patients with adverse reaction manifestations (ARM) and another group for patients with no ARM. The correlations with age, body mass index, alcohol drinking and smoking, underlying diseases, previous opioid usage and concurrently-administered drugs were analyzed for patients in these two groups. Results Of the total of 320 patients, 89 (27.8%) developed adverse reactions. Among these adverse reactions, constipation was manifested in 36 patients (11.3%); gastrointestinal illness in 27 (8.4%); nausea and vomiting in 24 (7.5%); dizziness in 12 (3.8%); drowsiness and mental confusion in 8 (2.5%); voiding difficulty in 7 (2.2%); skin reaction in 5 (0.6%) and other side effects in 31 (9.7%). Regarding factors associated with adverse reaction manifestations, multivariate analysis was conducted with two models: 1) opioid type and 2) concurrent administration of two or more opioids. The results showed that malignancy (OR=0.305, 95% CI=0.145-0.642) and prescription duration of ninety days more than longer (OR=2.127, 95% CI=1.137-3.980) were significant variables in opioid type. The occurrence rate of adverse reactions of morphine and that of oxycodone were 7.5 times (95% CI=2.547-22.208) and 7.3 times (95% CI= 2.545-20.701) greater than that of codeine. In concurrent administration of two or more opioids, malignancy (OR=0.323, 95% CI= 0.169-0.617), prescription duration of ninety days more than longer (OR=2.054, 95% CI=1.149-3.673) and GABA analogue (OR=3.259, 95% CI=1.777-5.977) were significant variables. The occurrence rate of adverse reactions of concurrent administration of two or more opioids was approximately 2.8 times (95% CI=1.089-7.163) greater than that of a single opioid drug. Conclusion In elderly male patients with opioid administration, factors that relatively lower development of adverse reactions were malignancy and codeine among opioids. The risk factors that comparatively increase the chance of having adverse reactions were long-term prescriptions, concurrent administration of GABA analogue, and taking of two or more opioids at the same time. Having a respective study is a limitation of this research, which necessitates a further investigation, including the associated components that had not been fully scrutinized in this study.