Background/Objectives: Dyspnea accompanies end-of-life in many cancer patients, with around 50% experiencing moderate/severe dyspnea, and is an independent factor for poor prognosis and declining quality of life. Managing dyspnea becomes a key component of palliative treatment and end-of-life support for cancer patients. Opioids seem to be the obvious choice in cancer patients as they also address the pain component (often important in such patients). Evidence-based conclusions on the effectiveness/safety of opioids in dyspnea management are scarce, and the results are still controversial. We aim to address this knowledge gap.Methods: In order to achieve the objective of this paper, we conducted a comprehensive search of international databases (PubMed, Medline, Embase, and Cochrane Library) for randomized controlled trials on the use of opioids to treat refractory dyspnea in adult cancer patients, and we performed a pooled meta-analysis of the results.Results: The effect of opioids on the relief of dyspnea was significant (SMD −0.44, 95% CI [−0.75,−0.12],p= 0.007). The significance of the opioid effect is maintained only for morphine administration (SMD −078, 95% CI [−1.45,−0.10],p= 0.02) and only for exertional dyspnea (SMD −1.00, 95% CI [−1.98, −0.03],p= 0.04). No correlation was noted between fentanyl/hydromorphone and dyspnea relief or opioids administered for dyspnea at rest. The subcutaneous route seems to be significantly correlated with dyspnea relief (SMD −0.73, 95% CI [−1.27, −0.19],p= 0.008), while the other administration modalities lack such an effect. No significant correlation was present between the usage of morphine/fentanyl and increased odds of severe adverse effects (OR 1.48, 95% CI [0.57,3.86],p= 0.42); however, fentanyl seems to be associated with increased somnolence. Although we aimed to evaluate how opioids impact the quality of life of cancer patients with dyspnea, we were unable to obtain such results due to the absolute lack of the literature available discussing QoL.Conclusions: Although we managed to provide some insights into the efficiency and safety of opioids usage for dyspnea management in cancer patients, the evidence based on the available literature is low grade. There is a marked need to address this knowledge gap with future high-quality studies with large sample sizes and standardized protocols.
背景/目的：呼吸困难是许多癌症患者临终阶段的伴随症状，约50%患者经历中重度呼吸困难，且是预后不良和生活质量下降的独立影响因素。呼吸困难管理已成为癌症患者姑息治疗和临终关怀的关键组成部分。阿片类药物因兼具镇痛作用（对此类患者常至关重要）而成为癌症患者的常用选择，但其在呼吸困难管理中的有效性及安全性循证结论匮乏，现有研究结果仍存争议。本研究旨在填补这一知识空白。 方法：为达成研究目标，我们系统检索了国际数据库（PubMed、Medline、Embase及Cochrane图书馆）中关于阿片类药物治疗成年癌症患者难治性呼吸困难的随机对照试验，并对结果进行荟萃分析。 结果：阿片类药物对呼吸困难缓解效果显著（标准化均数差SMD −0.44，95%置信区间[−0.75,−0.12]，p=0.007）。该显著性仅见于吗啡给药（SMD −0.78，95% CI [−1.45,−0.10]，p=0.02）及活动性呼吸困难（SMD −1.00，95% CI [−1.98,−0.03]，p=0.04）。芬太尼/氢吗啡酮与呼吸困难缓解无相关性，阿片类药物对静息性呼吸困难亦无显著改善。皮下给药途径与呼吸困难缓解显著相关（SMD −0.73，95% CI [−1.27,−0.19]，p=0.008），其他给药方式则无此效应。吗啡/芬太尼使用与严重不良反应风险增加无显著关联（比值比OR 1.48，95% CI [0.57,3.86]，p=0.42），但芬太尼可能增加嗜睡风险。尽管本研究旨在评估阿片类药物对伴呼吸困难癌症患者生活质量的影响，但因现有文献完全缺乏生活质量相关讨论，未能获得相应结果。 结论：虽然本研究初步揭示了阿片类药物在癌症患者呼吸困难管理中的效能与安全性，但基于现有文献的证据等级较低。亟需通过大样本量、标准化方案的高质量研究来填补这一知识空白。
A Systematic Review and Meta-Analysis on Opioid Management of Dyspnea in Cancer Patients
肿瘤(癌症)患者之家