Department of Medicine, Universidade Federal de São Paulo, São Paulo, Brazil.
Cochrane Brazil, Centro de Estudos de Saúde Baseada em Evidências e Avaliação Tecnológica em Saúde, São Paulo, Brazil.
Cochrane Database Syst Rev. 2023 Feb 1;2(2):CD013176. doi: 10.1002/14651858.CD013176.pub2.
Upper endoscopy is the definitive treatment for upper gastrointestinal haemorrhage (UGIH). However, up to 13% of people who undergo upper endoscopy will have incomplete visualisation of the gastric mucosa at presentation. Erythromycin acts as a motilin receptor agonist in the upper gastrointestinal (GI) tract and increases gastric emptying, which may lead to better quality of visualisation and improved treatment effectiveness. However, there is uncertainty about the benefits and harms of erythromycin in UGIH.
To evaluate the benefits and harms of erythromycin before endoscopy in adults with acute upper gastrointestinal haemorrhage, compared with any other treatment or no treatment/placebo.
We used standard, extensive Cochrane search methods. The latest search date was 15 October 2021.
We included randomised controlled trials (RCTs) that investigated erythromycin before endoscopy compared to any other treatment or no treatment/placebo before endoscopy in adults with acute UGIH.
We used standard Cochrane methods. Our primary outcomes were 1. UGIH-related mortality and 2. serious adverse events. Our secondary outcomes were 1. all-cause mortality, 2. visualisation of gastric mucosa, 3. non-serious adverse events, 4. rebleeding, 5. blood transfusion, and 5. rescue invasive intervention. We used GRADE criteria to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included 11 RCTs with 878 participants. The mean age ranged from 53.13 years to 64.5 years, and most participants were men (72.3%). One RCT included only non-variceal haemorrhage, one included only variceal haemorrhage, and eight included both aetiologies. We defined short-term outcomes as those occurring within one week of initial endoscopy. Erythromycin versus placebo Three RCTs (255 participants) compared erythromycin with placebo. There were no UGIH-related deaths. The evidence is very uncertain about the short-term effects of erythromycin compared with placebo on serious adverse events (risk difference (RD) -0.01, 95% confidence interval (CI) -0.04 to 0.02; 3 studies, 255 participants; very low certainty), all-cause mortality (RD 0.00, 95% CI -0.03 to 0.03; 3 studies, 255 participants; very low certainty), non-serious adverse events (RD 0.01, 95% CI -0.03 to 0.05; 3 studies, 255 participants; very low certainty), and rebleeding (risk ratio (RR) 0.63, 95% CI 0.13 to 2.90; 2 studies, 195 participants; very low certainty). Erythromycin may improve gastric mucosa visualisation (mean difference (MD) 3.63 points on 16-point ordinal scale, 95% CI 2.20 to 5.05; higher MD means better visualisation; 2 studies, 195 participants; low certainty). Erythromycin may also result in a slight reduction in blood transfusion (MD -0.44 standard units of blood, 95% CI -0.86 to -0.01; 3 studies, 255 participants; low certainty). Erythromycin plus nasogastric tube lavage versus no intervention/placebo plus nasogastric tube lavage Six RCTs (408 participants) compared erythromycin plus nasogastric tube lavage with no intervention/placebo plus nasogastric tube lavage. There were no UGIH-related deaths and no serious adverse events. The evidence is very uncertain about the short-term effects of erythromycin plus nasogastric tube lavage compared with no intervention/placebo plus nasogastric tube lavage on all-cause mortality (RD -0.02, 95% CI -0.08 to 0.03; 3 studies, 238 participants; very low certainty), visualisation of the gastric mucosa (standardised mean difference (SMD) 0.48 points on 10-point ordinal scale, 95% CI 0.10 to 0.85; higher SMD means better visualisation; 3 studies, 170 participants; very low certainty), non-serious adverse events (RD 0.00, 95% CI -0.05 to 0.05; 6 studies, 408 participants; very low certainty), rebleeding (RR 1.13, 95% CI 0.63 to 2.02; 1 study, 169 participants; very low certainty), and blood transfusion (MD -1.85 standard units of blood, 95% CI -4.34 to 0.64; 3 studies, 180 participants; very low certainty). Erythromycin versus nasogastric tube lavage Four RCTs (287 participants) compared erythromycin with nasogastric tube lavage. There were no UGIH-related deaths and no serious adverse events. The evidence is very uncertain about the short-term effects of erythromycin compared with nasogastric tube lavage on all-cause mortality (RD 0.02, 95% CI -0.05 to 0.08; 3 studies, 213 participants; very low certainty), visualisation of the gastric mucosa (RR 1.19, 95% CI 0.79 to 1.79; 2 studies, 198 participants; very low certainty), non-serious adverse events (RD -0.10, 95% CI -0.34 to 0.13; 3 studies, 213 participants; very low certainty), rebleeding (RR 0.77, 95% CI 0.40 to 1.49; 1 study, 169 participants; very low certainty), and blood transfusion (median 2 standard units of blood, interquartile range 0 to 4 in both groups; 1 study, 169 participants; very low certainty). Erythromycin plus nasogastric tube lavage versus metoclopramide plus nasogastric tube lavage One RCT (30 participants) compared erythromycin plus nasogastric tube lavage with metoclopramide plus nasogastric tube lavage. The evidence is very uncertain about the effects of erythromycin plus nasogastric tube lavage on all the reported outcomes (serious adverse events, visualisation of gastric mucosa, non-serious adverse events, and blood transfusion).
AUTHORS' CONCLUSIONS: We are unsure if erythromycin before endoscopy in people with UGIH has any clinical benefits or harms. However, erythromycin compared with placebo may improve gastric mucosa visualisation and result in a slight reduction in blood transfusion.
上消化道出血（UGIH）的明确治疗方法是上消化道内镜检查。然而，在接受上消化道内镜检查的人群中，多达 13%的人在上消化道内镜检查时胃黏膜的可视化不完全。红霉素在上消化道中充当胃动素受体激动剂，并增加胃排空，这可能导致更好的可视化质量和提高治疗效果。然而，在 UGIH 中，红霉素的益处和危害仍不确定。
评估在上消化道急性出血患者中，在上消化道内镜检查前使用红霉素与任何其他治疗或无治疗/安慰剂相比的益处和危害。
我们使用了标准的、广泛的 Cochrane 检索方法。最新的检索日期是 2021 年 10 月 15 日。
我们纳入了将红霉素与任何其他治疗或无治疗/安慰剂用于上消化道急性 UGIH 患者的随机对照试验（RCT）。
我们使用了标准的 Cochrane 方法。我们的主要结局是 1. UGIH 相关死亡率和 2. 严重不良事件。我们的次要结局是 1. 全因死亡率，2. 胃黏膜可视化，3. 非严重不良事件，4. 再出血，5. 输血，和 5. 抢救性侵入性干预。我们使用 GRADE 标准评估每个结局的证据确定性。
我们纳入了 11 项 RCT，共 878 名参与者。参与者的平均年龄范围为 53.13 岁至 64.5 岁，大多数参与者为男性（72.3%）。一项 RCT 仅包括非静脉曲张性出血，一项 RCT 仅包括静脉曲张性出血，八项 RCT 同时包括了这两种病因。我们将短期结局定义为在初始内镜检查后一周内发生的结局。
三项 RCT（255 名参与者）比较了红霉素与安慰剂。没有 UGIH 相关死亡。与安慰剂相比，红霉素在短期结局方面的严重不良事件（风险差（RD）-0.01，95%置信区间（CI）-0.04 至 0.02；3 项研究，255 名参与者；极低确定性）、全因死亡率（RD 0.00，95%CI-0.03 至 0.03；3 项研究，255 名参与者；极低确定性）、非严重不良事件（RD 0.01，95%CI-0.03 至 0.05；3 项研究，255 名参与者；极低确定性）和再出血（风险比（RR）0.63，95%CI0.13 至 2.90；2 项研究，195 名参与者；极低确定性）方面的证据非常不确定。红霉素可能改善胃黏膜可视化（平均差值（MD）2 分，16 分制；2 项研究，195 名参与者；低确定性）。红霉素也可能导致输血减少（MD-0.44 个单位的血液，95%CI-0.86 至-0.01；3 项研究，255 名参与者；低确定性）。
红霉素+鼻胃管灌洗与无干预/安慰剂+鼻胃管灌洗：六项 RCT（408 名参与者）比较了红霉素+鼻胃管灌洗与无干预/安慰剂+鼻胃管灌洗。没有 UGIH 相关死亡和严重不良事件。与无干预/安慰剂+鼻胃管灌洗相比，红霉素+鼻胃管灌洗在短期结局方面对全因死亡率（RD-0.02，95%CI-0.08 至 0.03；3 项研究，238 名参与者；极低确定性）、胃黏膜可视化（标准化均数差值（SMD）0.48 分，10 分制；SMD 越高，可视化越好；3 项研究，170 名参与者；极低确定性）、非严重不良事件（RD0.00，95%CI-0.05 至 0.05；6 项研究，408 名参与者；极低确定性）、再出血（RR1.13，95%CI0.63 至 2.02；1 项研究，169 名参与者；极低确定性）和输血（MD-1.85 个单位的血液，95%CI-4.34 至 0.64；3 项研究，180 名参与者；极低确定性）方面的证据非常不确定。
四项 RCT（287 名参与者）比较了红霉素与鼻胃管灌洗。没有 UGIH 相关死亡和严重不良事件。与鼻胃管灌洗相比，红霉素在短期结局方面的全因死亡率（RD0.02，95%CI-0.05 至 0.08；3 项研究，213 名参与者；极低确定性）、胃黏膜可视化（RR1.19，95%CI0.79 至 1.79；2 项研究，198 名参与者；极低确定性）、非严重不良事件（RD-0.10，95%CI-0.34 至 0.13；3 项研究，213 名参与者；极低确定性）、再出血（RR0.77，95%CI0.40 至 1.49；1 项研究，169 名参与者；极低确定性）和输血（中位数 2 个单位的血液，四分位距 0 至 4；1 项研究，169 名参与者；极低确定性）方面的证据非常不确定。
红霉素+鼻胃管灌洗与甲氧氯普胺+鼻胃管灌洗：一项 RCT（30 名参与者）比较了红霉素+鼻胃管灌洗与甲氧氯普胺+鼻胃管灌洗。与安慰剂相比，红霉素+鼻胃管灌洗对所有报告结局（严重不良事件、胃黏膜可视化、非严重不良事件和输血）的影响的证据不确定。
我们不确定上消化道内镜检查前使用红霉素对上消化道出血患者是否有任何临床益处或危害。然而，与安慰剂相比，红霉素可能改善胃黏膜可视化并减少输血。
