Centre for Evidence-Based Medicine, Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter, Woodstock Road, Oxford, OX2 6GG, UK.
Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter, Woodstock Road, Oxford, OX2 6GG, UK.
BMC Med. 2020 Mar 30;18(1):68. doi: 10.1186/s12916-020-01528-7.
The risks of harms from opioids increase substantially at high doses, and high-dose prescribing has increased in primary care. However, little is known about what leads to high-dose prescribing, and studies exploring this have not been synthesized. We, therefore, systematically synthesized factors associated with the prescribing of high-dose opioids in primary care.
We conducted a systematic review of observational studies in high-income countries that used patient-level primary care data and explored any factor(s) in people for whom opioids were prescribed, stratified by oral morphine equivalents (OME). We defined high doses as ≥ 90 OME mg/day. We searched MEDLINE, Embase, Web of Science, reference lists, forward citations, and conference proceedings from database inception to 5 April 2019. Two investigators independently screened studies, extracted data, and appraised the quality of included studies using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. We pooled data on factors using random effects meta-analyses and reported relative risks (RR) or mean differences with 95% confidence intervals (CI) where appropriate. We also performed a number needed to harm (NNT) calculation on factors when applicable.
We included six studies with a total of 4,248,119 participants taking opioids, of whom 3.64% (n = 154,749) were taking high doses. The majority of included studies (n = 4) were conducted in the USA, one in Australia and one in the UK. The largest study (n = 4,046,275) was from the USA. Included studies were graded as having fair to good quality evidence. The co-prescription of benzodiazepines (RR 3.27, 95% CI 1.32 to 8.13, I = 99.9%), depression (RR 1.38, 95% CI 1.27 to 1.51, I = 0%), emergency department visits (RR 1.53, 95% CI 1.46 to 1.61, I = 0%, NNT 15, 95% CI 12 to 20), unemployment (RR 1.44, 95% CI 1.27 to 1.63, I = 0%), and male gender (RR 1.21, 95% CI 1.14 to 1.28, I = 78.6%) were significantly associated with the prescribing of high-dose opioids in primary care.
High doses of opioids are associated with greater risks of harms. Associated factors such as the co-prescription of benzodiazepines and depression identify priority areas that should be considered when selecting, identifying, and managing people taking high-dose opioids in primary care. Coordinated strategies and services that promote the safe prescribing of opioids are needed.
PROSPERO, CRD42018088057.
阿片类药物的危害风险在高剂量时显著增加，而初级保健中的高剂量处方也有所增加。然而，对于导致高剂量处方的因素知之甚少，而且对此进行的研究尚未进行综合。因此，我们系统地综合了与初级保健中开具高剂量阿片类药物相关的因素。
我们对高收入国家的观察性研究进行了系统综述，这些研究使用了患者层面的初级保健数据，并探讨了处方阿片类药物患者的任何因素（分层为口服吗啡等效物（OME））。我们将高剂量定义为≥90 OME mg/天。我们从数据库建立到 2019 年 4 月 5 日，在 MEDLINE、Embase、Web of Science、参考文献列表、前向引文和会议论文集中进行了搜索。两名调查员独立筛选研究、提取数据，并使用观察性队列和病例对照研究的质量评估工具评估纳入研究的质量。我们使用随机效应荟萃分析汇总了与因素相关的数据，并在适当情况下报告了相对风险（RR）或均值差异及其 95%置信区间（CI）。对于适用的因素，我们还进行了危害需要人数（NNT）的计算。
我们纳入了 6 项研究，共纳入了 4248119 名服用阿片类药物的参与者，其中 3.64%（n=154749）服用高剂量药物。纳入的大多数研究（n=4）在美国进行，1 项在澳大利亚进行，1 项在英国进行。最大的研究（n=4046275）来自美国。纳入的研究被评为具有良好到中等质量的证据。共同处方苯二氮䓬类药物（RR 3.27，95%CI 1.32-8.13，I=99.9%）、抑郁（RR 1.38，95%CI 1.27-1.51，I=0%）、急诊就诊（RR 1.53，95%CI 1.46-1.61，I=0%，NNT 15，95%CI 12-20）、失业（RR 1.44，95%CI 1.27-1.63，I=0%）和男性性别（RR 1.21，95%CI 1.14-1.28，I=78.6%）与初级保健中开具高剂量阿片类药物显著相关。
高剂量阿片类药物与更大的危害风险相关。共同处方苯二氮䓬类药物和抑郁等相关因素确定了在初级保健中选择、识别和管理服用高剂量阿片类药物的人群时应考虑的优先领域。需要协调的策略和服务来促进阿片类药物的安全处方。
PROSPERO，CRD42018088057。
