Search and selection
Altogether, 1721 records were identified in the five databases, 904 in Embase, 211 in MEDLINE (via PubMed), 340 in CENTRAL, 101 in Scopus, and 165 in Web on Science. After duplicate removal, 1276 records remained for title and abstract selection. A total of 15 studies were assessed for full-text eligibility, of which six were excluded38,39,40,41,42,43. Five of the six excluded studies were duplicates but with different titles38,40,41,42,43, and one had an ineligible study design39. In addition, we identified 391 records through citation chasing, but only one study was sought for retrieval and was eligible for data extraction44. For more details on our search and selection process, see the PRISMA flowchart (Fig. 1).
PRISMA flowchart of the article selection process.
Basic characteristics of studies included
Our study consisted of 10 RCTs with a total of 1051 patients5,7,13,14,15,16,44,45,46,47. One of these studies was published as a conference abstract47. Five of the 10 studies focused on patients with non-variceal upper gastrointestinal bleeding (NVUGIB), mainly PUB13,16,45,46,47, whereas the other five focused on patients with VUGIB5,7,14,15,44. The studies were conducted in various geographical locations, five in Asia, three in Europe, one in Africa, and one in North America. More information on the trials, including their basic characteristics, can be found in (Table 1).
Early rebleeding (within 7 days)
We analyzed eight trials5,7,13,14,15,16,44,45 that reported rebleeding within seven days, involving 923 patients (465 in the EN group and 458 in the DN group). In the VUGIB subgroup, our analysis showed no significant difference between the two groups (RR 1.48, 95% CI 0.38–5.71), similarly in the PUB subgroup (RR 0.95, 95% CI 0.54–1.68). Overall, EN did not significantly or relevantly increase the risk of early rebleeding compared to DN (RR 1.04, 95% CI 0.66–1.63, p = 0.845, I2 = 0%, 95% CI 0–68%) (Fig. 2).
![figure 2](https://i0.wp.com/media.springernature.com/lw685/springer-static/image/art%3A10.1038%2Fs41598-024-61543-z/MediaObjects/41598_2024_61543_Fig2_HTML.png?resize=685%2C585&ssl=1)
Forest plot demonstrating the effect of early versus delayed nutrition on early rebleeding (within 7 days) after upper gastrointestinal bleeding. RR risk ratio, CI confidence interval.
Late rebleeding (within 30–42 days)
This analysis included eight studies5,7,14,15,16,44,46,47 that reported rebleeding within 30, 35, or 42 days, involving 693 patients (347 in the EN group and 346 in the DN group). The results were not statistically significant for either subgroup, including PUB (RR 1.14, 95% CI 0.16–7.98) and VUGIB (RR 1.13, 95% CI 0.40–3.17). Overall, EN did not increase the risk of late rebleeding compared to DN (RR 1.16, 95% CI 0.63–2.13, p = 0.583, I2 = 0%, 95% CI 0–68%) (Fig. 3).
![figure 3](https://i0.wp.com/media.springernature.com/lw685/springer-static/image/art%3A10.1038%2Fs41598-024-61543-z/MediaObjects/41598_2024_61543_Fig3_HTML.png?resize=685%2C590&ssl=1)
Forest plot demonstrating the effect of early versus delayed nutrition on late rebleeding (within 30–42 days) after upper gastrointestinal bleeding. RR risk ratio, CI confidence interval.
Early mortality (within 7 days)
Only five studies7,13,15,44,45 reporting mortality within seven days were included in this analysis, with a total of 543 patients (234 in the EN group and 229 in the DN group). There were no statistically significant differences between the studies in the PUB and VUGIB subgroups (RR 0.98, 95% CI 0.85–1.14, and RR 1.36, 95% CI 0.63–2.91, respectively). The overall effect was not statistically significant between the two groups (RR 1.20, 95% CI 0.85–1.71, p = 0.214, I2 = 0%, 95% CI 0–79%) (Fig. 4).
![figure 4](https://i0.wp.com/media.springernature.com/lw685/springer-static/image/art%3A10.1038%2Fs41598-024-61543-z/MediaObjects/41598_2024_61543_Fig4_HTML.png?resize=685%2C492&ssl=1)
Forest plot demonstrating the effect of early versus delayed nutrition on early mortality (within 7 days) after upper gastrointestinal bleeding. RR risk ratio, CI confidence interval.
Late mortality (within 30–42 days)
The analysis included seven studies5,7,14,15,16,44,47 that reported mortality within 30, 35, or 42 days. Altogether, 667 patients were involved (335 in the EN group and 332 in the DN group). There was no statistical difference in either subgroup; in the PUB subgroup (RR 0.51, 95% CI 0.03–7.83) and the VUGIB subgroup (RR 0.73, 95% CI 0.26–2.02). Overall, there was no statistically significant difference between the two groups; however, the results were clinically relevant with a tendency towards the EN group (RR 0.61, 95% CI 0.35–1.06, p = 0.072, I2 = 0%, 95% CI 0–71%) (Fig. 5).
![figure 5](https://i0.wp.com/media.springernature.com/lw685/springer-static/image/art%3A10.1038%2Fs41598-024-61543-z/MediaObjects/41598_2024_61543_Fig5_HTML.png?resize=685%2C572&ssl=1)
Forest plot demonstrating the effect of early versus delayed nutrition on late mortality (within 30–42 days) after upper gastrointestinal bleeding. RR risk ratio, CI confidence interval.
Length of hospital stay (days)
This analysis included six studies5,7,13,14,45,46 involving 570 patients (289 in the EN group and 281 in the DN group). In the PUB subgroup, there was no statistically significant difference between the two groups (MD: −1.34 days, 95% CI − 5.01 to 2.33), whereas in the VUGIB subgroup, EN significantly decreased LOS (MD −1.54 days, 95% CI −2.67 to −0.41). Overall, EN reduced the LOS compared to DN (MD −1.22 days, 95% CI −2.43 to −0.01, p = 0.049, I2 = 94%, 95% CI 90–97%) (Fig. 6).
![figure 6](https://i0.wp.com/media.springernature.com/lw685/springer-static/image/art%3A10.1038%2Fs41598-024-61543-z/MediaObjects/41598_2024_61543_Fig6_HTML.png?resize=685%2C504&ssl=1)
Forest plot demonstrating the effect of early versus delayed nutrition on the length of hospital stay after upper gastrointestinal bleeding. N number of patients in each arm, SD standard deviation, MD mean difference, CI confidence interval.
Jatin et al.15 and Gong et al.16 reported their results in medians instead of means. We decided to exclude those studies from our final analysis due to potentially biased results. However, even if we estimated the means from the provided medians, the findings indicate a significant reduction in LOS (MD −1.12 days, 95% CI −2.03 to −0.22, p = 0.022, I2 = 93%, 95% CI 88–96%) (Supplementary Material Fig. S1).
Blood transfusion requirement (units)
Seven studies5,7,13,14,16,45,46 reported transfusion requirement as an outcome; however, we could analyze only four studies (292 in the EN group and 286 in the DN group)5,16,45,46 due to heterogeneous definitions of this outcome among the included studies (summarized in the Supplementary Material Table S3). Overall, there was no statistically significant difference between the two groups (MD 0.00, 95% CI −0.04 to 0.05, p = 0.980, I2 = 0%, 95% CI 0–85%). (Supplementary Material Fig. S2).
Bacterial infection
Only three studies5,14,15 reported new-onset bacterial infections, including 251 patients (128 in the EN group and 123 in the DN group). Overall, there was no statistically significant difference between the two groups (RR 0.48, 95% CI 0.08–3.05, p = 0.229, I2 = 0%, 95% CI 0–90%) (Supplementary Material Fig. S3).
Ascites and hepatic encephalopathy
Three studies reported on new-onset ascites5,14,15. Overall, there was a tendency that ascites was more common in the DN group, however, it was not statistically significant (RR 0.64, 95% CI 0.34–1.20, p = 0.094, I2 = 0%, 95% CI 0–90%) (Supplementary Material Fig. S4). In addition, two studies5,15 reported on new-onset hepatic encephalopathy. (RR 1.03, 95% CI 0.50–2.11 and RR 0.75, 95% CI 0.18–3.14, respectively). We were not able to draw a statistical inference based on only two studies; therefore, we presented this outcome in the Supplementary Material Fig. S5 without an overall effect.
ICU admission and transfusion rate
We were not able to come to any statistical conclusions regarding these outcomes. Only one study45 reported the ICU admission days; there was no difference between the two groups (EN: 1.1 ± 0.2, DN: 1.1 ± 0.1), and one study15 reported the need for ICU admission (EN: 1/40, DN: 2/40). No studies reported data on the transfusion rate.
Risk of bias assessment and quality of evidence
In the articles, the randomization process and the selection of the reported result domains raised “some concerns”. Deviations from the planned intervention and missing outcome data had the lowest risk of bias. Bias from outcome measurement was high in LOS and new-onset hepatic encephalopathy outcomes. Results of risk of bias assessment for all the included studies by outcome are presented in the Supplementary Material Figs. S6–S12.
The quality of evidence was low or very low for all our outcomes. A summary table and explanation of the results can be found in the Supplementary Material (Supplementary Tables S4–S5).
Heterogeneity and publication bias
All analyses of the outcomes included showed negligible statistical heterogeneity levels (I2), with heterogeneity of 0% or less than 10%, except for the LOS outcome, which was 94% (CI 90–97%). This discrepancy may be attributed to variations in bleeding severity among patients, impacting hospitalization needs. We realized that when omitting Laine et al. study45 with leave-one-out sensitivity analysis, which included less severe patients compared to other studies, the effect size became more significant (MD −1.65 days, 95% CI −1.99 to − 1.31), and heterogeneity decreased to 5% (Supplementary Fig. S13–14). As for publication bias, the test’s diagnostic accuracy is limited for studies below 10, and as none of our analyses met this threshold, we opted to exclude this analysis.
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