In the present meta-analysis, we included 7 RCTs in the final analysis. Our results revealed that metoclopramide could improve the success rate of the post-pyloric placement of NETs; however, the evidence accumulated so far was insufficient. Furthermore, metoclopramide was found to facilitate the post-pyloric, post-D1, post-D2 and post-D3 placement of spiral NETs. Using metoclopramide in the short term for post-pyloric placement of NETs did not significantly increase the risk of adverse events.
As a conventional prokinetic agent, metoclopramide has a significant effect on the increase in antral contraction amplitude and the improvement of gastrointestinal peristalsis . Therefore, in theory, metoclopramide should be beneficial for the passage of NETs through the stomach and into the duodenum or jejunum. Unfortunately, neither Silva’s meta-analysis nor our results demonstrated the efficacy of metoclopramide, even though three RCTs were newly included in this updated meta-analysis. Several clinical heterogeneity deriving from participants (e.g., age, comorbidities, and concomitant medication) [28–30], operators (e.g., years of training, profession status, and educational degree of operators) [15, 31], intervention (e.g., the timing of medication, the dosage of metoclopramide, and the type of feeding tube) [12–18], outcome assessment (e.g., the follow-up period and the assessment personnel) [12–18] and the like, as well as insufficient sample sizes, may be liable for failing to establish metoclopramide’s beneficial effects.
In further subgroup analyses, we found that the administration of 20 mg metoclopramide had a significantly higher success rate of post-pyloric placement than did the administration of 10 mg metoclopramide. Although both 10 mg and 20 mg metoclopramide are plausible according to drug instruction, there has been a suggestion that metoclopramide displays disposition dose-dependency and obeys linear kinetics in individuals with intravenous or oral doses from 5 mg to 20 mg [32, 33]. Additionally, we found that the administration of metoclopramide prior to insertion could facilitate post-pyloric placement, while the interaction between subgroups did not reach statistical significance. Active gastric peristalsis at the time of feeding tube insertion is a key factor in achieving post-pyloric placement with metoclopramide . The insignificant interaction may be due to only one study that administered metoclopramide after insertion. With respect to the number of centers, the multicenter RCT with a large sample size may provide a more representational result, and the insignificant interaction may be due to only one study being designated as multicenter.
Recently, a novel NET with a spiral tip for post-pyloric placement in the assistance of prokinetic agents has emerged as a promising approach [18, 34–36], as demonstrated by the subgroup results stratified by spiral or straight tube tip. In previous studies, Lai et al. demonstrated that a spiral NET in conjunction with metoclopramide is preferable to a straight NET for post-pyloric placement . Additionally, a recent RCT also demonstrated the efficacy and safety of metoclopramide for the post-pyloric placement of spiral NETs . The spiral design may contribute to taking full advantage of gastrointestinal peristalsis to pass the tip through the pylorus and into the duodenum and jejunum . Furthermore, metoclopramide was found to facilitate the post-D1, post-D2 and post-D3 placement of spiral NETs. Thus, spiral feeding tubes may be more appropriate for post-pyloric placement if available. However, we failed to show a beneficial effect of metoclopramide on proximal jejunum placement, and there was significant between-study heterogeneity (I2 = 62%). This may be attributed to the relatively few cases in which tube tips could spontaneously migrate to the proximal jejunum even with the aid of metoclopramide and the impaired gastrointestinal function of the critically ill patients enrolled in their studies. However, given that few studies included in this meta-analysis focused on spiral NETs, the beneficial effects of metoclopramide on post-pyloric, post-D1, post-D2, post-D3, and proximal jejunum placement warrant further investigation.
With regard to safety, concern about the use of metoclopramide has been expressed because of its potential role in causing adverse events . Some investigators felt an increase in dose to 20 mg intravenously would run the risk of an increased incidence of side effects. However, the adverse events participants encountered were minimal and mild with no need for special treatment. Additionally, our results showed that there was no significant difference between the metoclopramide and control groups either in drug side effects or tube insertion complications. Therefore, metoclopramide may be safe in a regular dose of no more than 20 mg in the short term for the post-pyloric placement of NETs when more attention has been paid to its contraindications (e.g., patients in epilepsy and renal or liver dysfunction) to avoid severe adverse events.
Although this meta-analysis did not demonstrate metoclopramide’s beneficial effects on the post-pyloric placement of NETs, several pivotal modifications to Silva’s meta-analysis  had been made. First, we have included three additional studies, of which Paz’s study  was identified by reviewing the full text after retrieving it from the English database. Chen’s study  was retrieved from the Chinese database, and Hu’s study  was obtained from the updated English database. Then, this meta-analysis doubled the sample size compared with Silva’s meta-analysis. Third, we have more resourceful outcome analyses, including post-D1, post-D2, post-D3 and proximal jejunum placement and adverse events involving drug side effects and tube insertion complications. Additionally, more subgroup analyses, sensitivity analyses, and publication bias were also performed for the primary outcomes. Notably, the TSA was performed to evaluate the reliability of the conclusion. Finally, we found that metoclopramide might be beneficial for the post-pyloric placement of spiral NETs. More RCTs are necessary to confirm this finding.
Additionally, there were several limitations worth noting. First, some studies were at high risk of bias, and moderate statistical heterogeneity was present in the primary outcomes, which influenced the quality of evidence and the interpretation of findings. Second, the follow-up period in the included studies was not consistent, ranging from 30 minutes to 24 hours after insertion. Third, the results of secondary outcomes and subgroup analyses might only serve as a useful hint for metoclopramide’s beneficial effects on the post-pyloric placement of spiral NETs because relatively few studies provided accurate locations of the feeding tube tip. Finally, the overall quality of the evidence was low; thus, the negative results of metoclopramide for post-pyloric placement should be considered with caution.