Electromagnetic-Guided Versus Endoscopic Placement of Nasoenteral Feeding Tubes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objectives: Current evidence supporting the utility of electromagnetic (EM)-guided method as the preferred technique for nasoenteral feeding tube placement is limited. We conducted a meta-analysis to compare the performance of EM-guided versus endoscopic placement. Methods: We searched several databases for all randomized controlled trials evaluating the EM-guided vs. endoscopic placement of nasoenteral feeding tubes up to 28 July 2020. Primary outcome was procedure success rate. Secondary outcomes included reinsertion rate, number of attempts, placement-related complications, tube-related complications, insertion time, total procedure time, patient discomfort, recommendation scores, length of hospital stay, mortality, and total costs. Results: Four trials involving 536 patients were qualied for the nal analysis. There was no difference between the two groups in procedure success rate (RR 0.97; 95% CI: 0.91-1.03), reinsertion rate (RR 0.84; 95% CI: 0.59-1.20), number of attempts (WMD -0.23; 95% CI: -0.99-0.53), placement-related complications (RR 0.78; 95% CI: 0.41-1.49), tube-related complications (RR 1.08; 95% CI: 0.82-1.44), total procedure time (WMD -18.09; 95% CI: -38.66-2.47), length of hospital stay (WMD 1.57; 95% CI: -0.33-3.47), ICU mortality (RR 0.80; 95% CI: 0.50-1.29), in-hospital mortality (RR 0.87; 95% CI: 0.59-1.28), and total costs (SMD -1.80; 95% CI: -3.96-0.36). The EM group was associated with longer insertion time (WMD 4.3; 95% CI: 0.2-8.39), higher patient discomfort level (WMD 1.28; 95% CI: 0.46-2.1), and higher recommendation scores (WMD 1.67; 95% CI: 0.24-3.10). Conclusions: EM-guided placement showed similar ecacy, safety and cost-effectiveness when compared with endoscopic placement of nasoenteral feeding tubes.


Introduction
Malnutrition and inability to eat are conditions often encountered in inpatients. For such patients, enteral nutrition is considered to be superior to parenteral nutrition since it reduces complications, improves patient outcome, and is more cheaper [1,2]. It is common practice to place a nasoenteral feeding tube for enteral nutrition in patients who are intolerant of intragastric nutrition [3]. Endoscopic technique is typically used, but requires patient transportation between wards, preprocedural fasting, and radiological con rmation of the tube's position. Since rst reported by Phang et al. in 2006[4], electromagnetic (EM)-guided technique has been increasingly used for nasoenteral feeding tube placement. It has been suggested to be convenient and lead to a signi cant cost reduction.
With increasing availability and familiarity with this technique, several randomized controlled trials (RCTs ) [5][6][7][8] have compared EM-guided versus endoscopic (ENDO) technique. These RCTs were limited because of small sample sizes. We therefore conducted a meta-analysis to compare the performance between EM and ENDO.

Methods
This meta-analysis follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement [9], and was registered on PROSPERO (CRD42020172427).

Search strategy
Two investigators (Y-W and Y-Z) independently searched MEDLINE, EMBASE, the Cochrane Library, and Google Scholar for all entries through 28 July 2020 using the following search terms: "Cortrak", "electromagnetic", "endoscopic", "nasoenteral, or post-pyloric", and "tube(s), feeding, or nutrition". (see Supplemental Digital Content 1, for exemplar PubMed search) Then, they compared their lists of potentially eligible titles and abstracts and achieved a consensus on full review.

Study selection criteria
The following criteria were used to select studies for inclusion: (i) studies directly compared EM-guided versus endoscopic placement of nasoenteral feeding tubes; (ii) RCTs; and (iii) were English language articles. All retrospective studies, non-controlled studies, reviews, case series, abstracts, editorials, letters to editor, animal studies, duplicate studies and studies without data on any of the primary or secondary outcomes were excluded.

Study selection and data extraction
Decisions about study inclusion and exclusion were made independently by two Investigators (Y-W and W-H). Two investigators (Z-J and W-H) extracted data independently from each study. We collected author, year of publication, country of origin, number of centers, participating operators, patient demographics, indications for enteral nutrition, and study outcomes. Any discrepancies were resolved by mutual discussion.

Outcome measures
Our primary outcome was procedure success rate (de ned as the percentage of successful tube placement in the desired location as determined). Secondary outcomes included reinsertion rate (de ned as the percentage of patients undergoing reinsertion after an unsuccessful primary procedure or dislodgement/blockage of the tube), number of attempts, placement-related complications, tube-related complications, insertion time (de ned as the time interval from insertion of the tube until xation of the tube to the nostrils), total procedure time (including time for preparation and recovery), patient discomfort (recorded with scores in the range 0 [no complaints] to 10 [maximum complaints]), patient recommendation (recorded with scores in the range 0 [not recommended] to 10 [highly recommended]), length of hospital stay, intensive care unit (ICU) mortality, in-hospital mortality, total costs (including the costs for tube placement procedure, complications and therapeutic interventions).

Assessment of methodological quality
Risk of bias assessment of RCTs was performed independently by two investigators (Y-W and Z-J) using the Cochrane Collaboration' s tool [10]. Any disagreements were resolved by consensus after a mutual discussion.

Statistical analysis
Risk ratios (RRs) were calculated for categorical variables. Studies with no events in both arms were excluded from the meta-analysis of RRs [11]. Standard mean differences (SMDs) were calculated for continuous variables including total costs based on different monetary units. Weighted mean differences (WMDs) were calculated for the rest of continuous variables. In cases of missing data, especially for continuous variables, we estimated the mean and standard deviation from the sample size, median, range, and/or interquartile range, if available, according to the approximation method previously validated [12]. Owning to variation in study protocols and study populations, a random effects model for all analyses was used [11]. Heterogeneity among studies was assessed by calculating the I 2 statistics and tested using the Cochrane Q-test [13]. Subgroup analyses were performed for all outcomes based on: a) study setting (single-vs. multi-center), b) geographical location (Asia vs. Europe), c) the BMI level of patients with the validated method (ENDO group) (< 25 vs. >25), d) prior altered upper gastrointestinal anatomy (with vs. without), e) patient population (critically ill vs. non-critically ill patients). For those subgroups with only one study included, subgroup analyses were not performed. We had planned that if enough studies (≥ 10) were included in the analysis of primary outcome, we would construct a funnel plot to evaluate publication bias [11], otherwise, the Egger's test was applied [14]. Statistical analyses were performed using Review Manager 5.3 (The Cochrane Collaboration, The Nordic Cochrane Centre, Copenhagen, Denmark).

Search strategy yield and study characteristics
The search identi ed 176 potentially relevant studies, 15 of which were examined in detail and 4 RCTs of which were included in the nal analysis [5][6][7][8].
( Fig. 1) A total of 536 patients were included, of which 287 were in EM group and 249 in ENDO group. Mean age was 57.1 years with a range of 51.5 to 64.6 years. The sex distribution was 53.3% male patients, with a range of 51.3-63.6%. Two studies were conducted in Netherlands [5][6][7][8], one in Austria [5], and one in China [8]. Two of the studies [6,7] were of multi-center design (3 or 5 recruiting sites). Two studies exclusively evaluated critical ill patients, one [6] evaluated patients from gastrointestinal surgical wards, and the remaining one [7] included outpatients, ward patients, and critically ill patients. In ENDO group, tube placement was performed by a gastroenterologist assisted by one or two nurses. For EM group, tube placement was performed by one nurse in two studies [6,7], by a nutritional support team in one study [8], and the remaining one study [5] did not specify this issue. One study [6] included patients with prior altered upper gastrointestinal anatomy and the remaining three studies did not. For EM technique, pre-procedural fasting was required in one study [7], not required in one study [6], and the remaining two studies [5,8] did not specify this issue. Conscious sedation in EM group was not required in two studies [6,8], but was used if indicated in the remaining two studies. For ENDO group, conscious sedation was used in a large portion of patients. Details of the characteristics of included studies are given in Table 1. RCT, randomized controlled trial; EM, electromagnetic-guided nasoenteral feeding tube placement; ENDO, endoscopic nasoenteral feeding tube placement; GE reported.

Quality assessment
All of the included studies had a high risk of performance bias. This could not be avoided because the operators and patients could not be blinded to the method of examination. There was unclear risk of detection bias in all studies, as blinding of outcome assessment could only be done for subjective outcomes such as patient discomfort and patient recommendation. One study [5] (Fig. 2a). We did not employ funnel plot to access for publication bias as fewer than 10 studies were included. There was no evidence of publication bias by Egger' s test for the primary outcome (P = 0.18).

Subgroup analyses
Subgroup analyses were performed for all outcomes. (Supplemental Digital Content 3) EM compared with ENDO was associated with lower total cost when only evaluating multicenter RCTs. (WMD − 0.29; 95% CI: -0.51-0.06; P = 0.01, I² = 0%). Other subgroup analysis results were accordant to the main analyses. Heterogeneity was reduced when subgroup analyses for total costs and insertion time was performed using level of BMI < 25 as a modi er. The other heterogeneity could not be explained by these variables with the available data.

Discussion
The conventional methods for the placement of nasoenteral feeding tubes include blind, uoroscopic, and endoscopic methods [15,16]. The gold standard is the endoscopic technique, which has success rates above 90% [17,18]. Bed-side EM-guided tube placement can be performed in recent years [19]. This has several potential advantages compared with endoscopic placement because only one trained nurse and less equipment is needed [20,21]. EM and ENDO technique have been compared in only one systematic review until now [22]. That review by Gerritsen et al. involving only one relevant RCT (66 patients) concluded that the e cacy and safety of the two techniques did not differ signi cantly, but EM offered advantages in logistics. In view of 3 new RCTs published, we have attempted to pool the evidence to further evaluate the performance of EM vs. ENDO.
Regarding treatment success, our meta-analysis demonstrated that no difference existed in procedure success rate, reinsertion rate, and number of attempts. These results were robust across the subgroup analyses. Our procedure success rates of the two groups (82.6% vs. 83.1%) were lower than those reported in the previous systematic review (85% vs. 89%), and our reinsertion rates (27.7% vs. 33.1%) were higher than theirs (21% vs. 16%). The reasonable explain may be that our review included many gastrointestinal disease patients, with an altered upper gastrointestinal anatomy, which may hamper tube placement.
With respect to safety, we found that, complication rates, length of hospital stay, ICU mortality and in-hospital mortality were similar for both techniques. Subgroup analysis results were consistent with main analyses in these outcomes. Average placement-and tube-related complication rates for EM that have been reported in previous review was 0.4% and 15%, our nding (6.3% and 35.4%) was signi cantly higher than theirs. The most common complications in our review were epistaxis and dislodgment/blockage of the tube. However, undetected statistical difference in complications may be attributed to low incidence and insu cient sample size. More large-sample RCTs are required to investigate these outcomes in greater detail. It is worth noting that, unlike EM, sedation is often required during endoscopic technique. Sedation is associated with a small risk of cardiopulmonary adverse events, e.g., hypoxia [23]. This could account for the difference in hypoxia incidence between the two techniques (0.3% vs. 1.6%).
Although EM was more time consuming for insertion, the fact that EM technique does not require sedation and patient transportation resulted in comparable total time compared with endoscopy. Another advantage of EM is that in case of partial migration of the tube, repositioning of the tube can be done by reinserting the stylet through the tube at the bedside, whereas repositioning by endoscopy would require removal of the tube and repetition of the entire procedure (including sedation). Regarding patient-reported outcomes, patients reported more discomfort during EM-guided placement than during endoscopy. This nding is probably related to the large differences in the use of conscious sedation between the two groups. On the other hand, recommendation scores were signi cantly higher in EM group, presumably because the discomfort is not bothersome enough to advise others not to undergo the EM procedure. This supports the hypothesis that EM is a more patient-friendly approach.
Finally, as for total costs, no signi cant difference was found between the two groups. The reduction in the use of hospital resources (e.g., personnel, patient transportation), and the absence of the need for sedation and radiographic con rmation can lead to a reduction in costs. Therefore, the cost difference between EM and ENDO we found may be an underestimation of the true cost difference. This could also be evidenced in subgroup analyses: lower total cost with EM was noted, when only evaluating multicenter RCTs. More well-designed multicenter RCTs are therefore warranted.
Our meta-analysis has several strengths. First, we conducted rigorous search of the RCTs and added 3 additional studies that the previous systematic review did not include. Second, comprehensive subgroup analyses were performed. Last, we assessed multiple clinically relevant outcomes. Because critically ill and non-critically ill patients were both included, the results of our review are probably generalizable to the overall hospital population. However, limitations are present and are as follows. The number of included studies is relatively small. Variation among studies was observed in study design, introducing heterogeneity. Data on patients with prior altered upper gastrointestinal anatomy was not enough for subgroup analyses.

Conclusion
Based on the currently available literature, EM-guided nasoenteral feeding tube placement appears to be as safe, effective, and cost-effective as endoscopic placement while offering some distinct advantages. EM may be considered the preferred technique for nasoenteral feeding tube placement. Further studies are needed to con rm our ndings.        Forest plots for (a) insertion time; (b) total procedure time; (c) patient discomfort; (d) patient recommendation between EM and ENDO.

Figure 5
Forest plots for (a) length of hospital stay, (b) ICU mortality, (c) in-hospital mortality, and (d) total costs of the feeding tube placement between EM and ENDO.

Figure 5
Forest plots for (a) length of hospital stay, (b) ICU mortality, (c) in-hospital mortality, and (d) total costs of the feeding tube placement between EM and ENDO.

Supplementary Files
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