Deckx Laura, De Sutter An Im, Guo Linda, Mir Nabiel A, van Driel Mieke L
Discipline of General Practice, School of Medicine, The University of Queensland, Building 16/910, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia, 4029.
Cochrane Database Syst Rev. 2016 Oct 17;10(10):CD009612. doi: 10.1002/14651858.CD009612.pub2.
Many treatments for the common cold exist and are sold over-the-counter. Nevertheless, evidence on the effectiveness and safety of nasal decongestants is limited.
To assess the efficacy, and short- and long-term safety, of nasal decongestants used in monotherapy to alleviate symptoms of the common cold in adults and children.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 6, June 2016), which contains the Cochrane Acute Respiratory Infections (ARI) Specialised Register, MEDLINE (1946 to July 2016), Embase (2010 to 15 July 2016), CINAHL (1981 to 15 July 2016), LILACS (1982 to July 2016), Web of Science (1955 to July 2016) and clinical trials registers.
Randomised controlled trials (RCTs) and cluster-RCTs investigating the effectiveness and adverse effects of nasal decongestants compared with placebo for treating the common cold in adults and children. We excluded quasi-RCTs.
Three review authors independently extracted and summarised data on subjective measures of nasal congestion, overall patient well-being score, objective measures of nasal airway resistance, adverse effects and general recovery. One review author acted as arbiter in cases of disagreement. We categorised trials as single and multi-dose and analysed data both separately and together. We also analysed studies using an oral or topical nasal decongestant separately and together.
We included 15 trials with 1838 participants. Fourteen studies included adult participants only (aged 18 years and over). In six studies the intervention was a single dose and in nine studies multiple doses were used. Nine studies used pseudoephedrine and three studies used oxymetazoline. Other decongestants included phenylpropanolamine, norephedrine and xylometazoline. Phenylpropanolamine (or norephedrine) is no longer available on the market therefore we did not include the results of these studies in the meta-analyses. Eleven studies used oral decongestants; four studies used topical decongestants.Participants were included after contracting the common cold. The duration of symptoms differed among studies; in 10 studies participants had symptoms for less than three days, in three studies symptoms were present for less than five days, one study counted the number of colds over one year, and one study experimentally induced the common cold. In the single-dose studies, the effectiveness of a nasal decongestant was measured on the same day, whereas the follow-up in multi-dose studies ranged between one and 10 days.Most studies were conducted in university settings (N = eight), six at a specific university common cold centre. Three studies were conducted at a university in collaboration with a hospital and two in a hospital only setting. In two studies the setting was unclear.There were large differences in the reporting of outcomes and the reporting of methods in most studies was limited. Therefore, we judged most studies to be at low or unclear risk of bias. Pooling was possible for a limited number of studies only; measures of effect are expressed as standardised mean differences (SMDs). A positive SMD represents an improvement in congestion. There is no defined minimal clinically important difference for measures of subjective improvement in nasal congestion, therefore we used the SMDs as a guide to assess whether an effect was small (0.2 to 0.49), moderate (0.5 to 0.79) or large (≥ 0.8).Single-dose decongestant versus placebo: 10 studies compared a single dose of nasal decongestant with placebo and their effectiveness was tested between 15 minutes and 10 hours after dosing. Seven of 10 studies reported subjective symptom scores for nasal congestion; none reported overall patient well-being. However, pooling was not possible due to the large diversity in the measurement and reporting of symptoms of congestion. Two studies recorded adverse events. Both studies used an oral decongestant and each of them showed that there was no statistical difference between the number of adverse events in the treatment group versus the placebo group.Multi-dose decongestant versus placebo: nine studies compared multiple doses of nasal decongestants with placebo, but only five reported on the primary outcome, subjective symptom scores for nasal congestion. Only one study used a topical decongestant; none reported overall patient well-being. Subjective measures of congestion were significantly better for the treatment group compared with placebo approximately three hours after the last dose (SMD 0.49, 95% confidence interval (CI) 0.07 to 0.92; P = 0.02; GRADE: low-quality evidence). However, the SMD of 0.49 only indicates a small clinical effect. Pooling was based on two studies, one oral and one topical, therefore we were unable to assess the effects of oral and topical decongestants separately. Seven studies reported adverse events (six oral and one topical decongestant); meta-analysis showed that there was no statistical difference between the number of adverse events in the treatment group (125 per 1000) compared to the placebo group (126 per 1000). The odds ratio (OR) for adverse events in the treatment group was 0.98 (95% CI 0.68 to 1.40; P = 0.90; GRADE: low-quality evidence). The results remained the same when we only considered studies using an oral decongestant (OR 0.95, 95% CI 0.65 to 1.39; P = 0.80; GRADE: low-quality evidence).
AUTHORS' CONCLUSIONS: We were unable to draw conclusions on the effectiveness of single-dose nasal decongestants due to the limited evidence available. For multiple doses of nasal decongestants, the current evidence suggests that these may have a small positive effect on subjective measures of nasal congestion in adults with the common cold. However, the clinical relevance of this small effect is unknown and there is insufficient good-quality evidence to draw any firm conclusions. Due to the small number of studies that used a topical nasal decongestant, we were also unable to draw conclusions on the effectiveness of oral versus topical decongestants. Nasal decongestants do not seem to increase the risk of adverse events in adults in the short term. The effectiveness and safety of nasal decongestants in children and the clinical relevance of their small effect in adults is yet to be determined.
普通感冒有多种治疗方法且可在柜台购买。然而，关于鼻减充血剂有效性和安全性的证据有限。
评估单药使用鼻减充血剂缓解成人和儿童普通感冒症状的疗效及短期和长期安全性。
我们检索了Cochrane对照试验中心注册库（CENTRAL，2016年第6期），其中包含Cochrane急性呼吸道感染（ARI）专业注册库、MEDLINE（1946年至2016年7月）、Embase（2010年至2016年7月15日）、CINAHL（1981年至2016年7月15日）、LILACS（1982年至2016年7月）、Web of Science（1955年至2016年7月）以及临床试验注册库。
随机对照试验（RCT）和整群RCT，研究鼻减充血剂与安慰剂相比治疗成人和儿童普通感冒的有效性和不良反应。我们排除了半随机对照试验。
三位综述作者独立提取并汇总关于鼻充血主观测量、患者总体健康评分、鼻气道阻力客观测量、不良反应和总体恢复的数据。如有分歧，由一位综述作者担任仲裁。我们将试验分为单剂量和多剂量，并分别和综合分析数据。我们还分别和综合分析使用口服或局部鼻减充血剂的研究。
我们纳入了15项试验，共1838名参与者。14项研究仅纳入了成年参与者（18岁及以上）。6项研究的干预为单剂量，9项研究使用了多剂量。9项研究使用了伪麻黄碱，3项研究使用了羟甲唑啉。其他减充血剂包括苯丙醇胺、去甲麻黄碱和赛洛唑啉。苯丙醇胺（或去甲麻黄碱）已不再上市，因此我们未将这些研究结果纳入荟萃分析。11项研究使用口服减充血剂；4项研究使用局部减充血剂。参与者在患普通感冒后被纳入。各研究中症状持续时间不同；10项研究中参与者症状持续不到三天，3项研究中症状持续不到五天，1项研究统计了一年中的感冒次数，1项研究通过实验诱发普通感冒。在单剂量研究中，在给药当天测量鼻减充血剂的有效性，而多剂量研究的随访时间为1至10天。大多数研究在大学环境中进行（N = 8），6项在特定大学普通感冒中心进行。3项研究由大学与医院合作进行，2项仅在医院环境中进行。2项研究的环境不明确。大多数研究在结果报告方面存在很大差异，且方法报告有限。因此，我们判断大多数研究存在低或不明确的偏倚风险。仅对少数研究进行了合并分析；效应量以标准化均数差（SMD）表示。正的SMD表示充血改善。对于鼻充血主观改善测量，没有明确的最小临床重要差异，因此我们使用SMD作为评估效应是小（0.2至0.49）、中等（0.5至0.79）还是大（≥0.8）的指南。
10项研究比较了单剂量鼻减充血剂与安慰剂，并在给药后15分钟至10小时测试其有效性。10项研究中的7项报告了鼻充血的主观症状评分；均未报告患者总体健康状况。然而，由于充血症状测量和报告的巨大差异，无法进行合并分析。2项研究记录了不良事件。两项研究均使用口服减充血剂，且每项研究均表明治疗组与安慰剂组的不良事件数量无统计学差异。
9项研究比较了多剂量鼻减充血剂与安慰剂，但仅5项报告了主要结局，即鼻充血的主观症状评分。仅一项研究使用局部减充血剂；均未报告患者总体健康状况。与安慰剂相比，治疗组在最后一剂后约三小时的充血主观测量明显更好（SMD 0.49，95%置信区间（CI）0.０７至0.92；P = 0.02；GRADE：低质量证据）。然而，0.49的SMD仅表明临床效果较小。合并分析基于两项研究，一项口服和一项局部，因此我们无法分别评估口服和局部减充血剂的效果。7项研究报告了不良事件（6项口服和1项局部减充血剂）；荟萃分析表明，治疗组（每1000人中有125例）与安慰剂组（每1000人中有126例）的不良事件数量无统计学差异。治疗组不良事件的比值比（OR）为0.98（95%CI 0.68至1.40；P = 0.90；GRADE：低质量证据）。当我们仅考虑使用口服减充血剂的研究时，结果保持不变（OR 0.95，95%CI 0.65至１.39；P = 0.80；GRADE：低质量证据）。
由于现有证据有限，我们无法就单剂量鼻减充血剂的有效性得出结论。对于多剂量鼻减充血剂，目前的证据表明，这些药物可能对患普通感冒的成年人鼻充血主观测量有小的积极作用。然而，这种小作用的临床相关性尚不清楚，且没有足够的高质量证据得出任何确凿结论。由于使用局部鼻减充血剂的研究数量较少，我们也无法就口服与局部减充血剂的有效性得出结论。鼻减充血剂短期内似乎不会增加成年人不良事件的风险。鼻减充血剂在儿童中的有效性和安全性以及其在成年人中较小作用的临床相关性尚待确定。
