Long-term Health Effects of Antipyretic Drug Use in the Ageing Population: A Systematic Review

Background: It is unclear whether fever suppression is beneficial or harmful in the long term in the elderly, due to different immune profile and body temperature compared to the young. Our objective was to determine the long-term health effects of antipyretic treatment in the elderly during infections.Methods: a systematic review was carried out including studies investigating antipyretic treatment during infections, comparing with any other drug/therapy/placebo/none. PubMed, Embase and Cochrane CENTRAL databases were searched. Primary and secondary outcomes were onset or worsening of chronic inflammatory diseases, and fever reduction, length of hospital stay, patient satisfaction, mortality, laboratory parameters indicative of morbidity and progress to complications respectively.Results: Of 11481, studies,17 (2 RCTs, 7 observational, 1 case series and 7 case reports) were included for the review. None investigated the primary outcome and patient-reported outcomes.Risk-of-bias of studies was unclear to high in the included studies. Narrative synthesis was performed as meta-analysis was impossible owing to heterogeneity of the included studies.Antipyretics showed significant reduction of fever in the RCTs. Five studies reported significant drop in BP and one study showed significant mortality from the antipyretics. Morbidity indicators and length of stay were available only in the studies that reported adverse events. Certainty of evidence (GRADE) was low to very low for all outcomes.Conclusions: Evidence regarding long term benefit or harm from fever suppression with antipyretics during infections in the elderly is insufficient.背景：由于老年人与年轻人的免疫特征及体温存在差异，目前尚不明确退热治疗对老年人的长期健康有益还是有害。本研究旨在明确老年人感染期间接受退热治疗对其长期健康的影响。 方法：本研究开展了一项系统综述，纳入所有探究老年人感染期间退热治疗的研究，并将其与其他药物、疗法、安慰剂或不干预措施进行对比。检索了PubMed、Embase及Cochrane CENTRAL数据库。主要结局指标为慢性炎症性疾病的发生或恶化；次要结局指标依次为体温降低幅度、住院时长、患者满意度、死亡率、反映发病情况的实验室指标以及并发症发生进展情况。 结果：初筛共获得11481项研究，最终纳入17项（其中2项随机对照试验（Randomized Controlled Trial, RCT）、7项观察性研究、1项病例系列研究及7项病例报告）进行本综述。纳入研究均未对主要结局指标及患者报告结局进行探究。纳入研究的偏倚风险为不确定至高风险水平。由于纳入研究存在异质性，无法开展荟萃分析，因此采用描述性综合进行结果分析。在随机对照试验中，退热药物可显著降低体温。5项研究报告退热治疗可导致血压（Blood Pressure, BP）显著下降，另有1项研究显示退热药物与显著死亡率升高相关。发病相关指标及住院时长仅在报告不良事件的研究中有所涉及。所有结局指标的证据确定性（推荐分级的评估、制订与评价，Grading of Recommendations Assessment, Development and Evaluation, GRADE）均为低至极低水平。 结论：目前尚无足够证据表明老年人感染期间接受退热药物抑制体温可带来长期获益或产生不良影响。