Should Prophylactic Endotracheal Intubation Be Performed in Upper Gastrointestinal Bleeding?

No consensus exists on the standard of intraoperative airway management approach to prevent endoscopy complications in acute gastrointestinal (GI) bleeding. Eight years after our initial meta-analysis, we reassessed the effect of prophylactic endotracheal intubation in acute GI bleeding in hospitalized patients. Multiple databases were reviewed in 2024, identifying 10 studies that compared prophylactic endotracheal intubation (PEI) versus no intubation in acute upper GI bleeding in hospitalized patients. Outcomes of interest included pneumonia, length of hospital stay, aspiration, and mortality. The odds ratio (OR) or mean difference (MD) using the random effects model was calculated for each outcome. In total, 11 studies (10 retrospective, one prospective) were included in the meta-analysis (n = 7,332). PEI demonstrated statistically significant higher odds of pneumonia (OR = 5.83; 95% confidence interval (CI) = 3.15-10.79; p < 0.01) and longer length of stays (MD = 0.84; 95% CI = 0.12-1.56; p = 0.02). However, mortality (OR = 1.68; 95% CI = 0.78-3.64; p = 0.19) and aspiration (OR = 2.79; 95% CI = 0.89-8.7; p = 0.08) were not statistically significant. PEI before esophagogastroduodenoscopy for hospitalized upper GI bleeding patients is associated with an increased incidence of pneumonia within 48 hours and prolonged hospitalization but no statistically significant increased risk of mortality or aspiration.


Introduction And Background
Upper gastrointestinal bleeding (UGIB) is a prevalent and serious global health issue, resulting in around 350,000 hospital admissions annually in the United States alone [1].Peptic ulcer disease (PUD) and variceal bleeding are among the leading causes of UGIB.Despite advances in medicine, UGIB continues to be linked with high mortality rates, reaching up to 10% and 20% for variceal and non-variceal bleeding cases, respectively [2].Esophagogastroduodenoscopy (EGD) is currently the standard diagnostic and therapeutic tool for managing UGIB [3].
Although EGD is generally considered safe in the average-risk population, with low complication and mortality rates, the risk may be altered in the setting of UGIB.Cardiopulmonary complications are of particular concern, accounting for a significant proportion of all adverse events and fatalities.Intraoperative aspiration of blood and gastric contents is thought to be a frequent cause of these complications [4,5].
Endoscopists and intensivists often recommend prophylactic endotracheal intubation (PEI) to avert the triggering aspiration event.However, critically ill patients with UGIB are complex and have the potential for hemodynamic instability, rendering this practice contentious [3].The lack of supporting evidence remains the most significant obstacle to the safe, efficient, and effective management of such patients [6].Bearing this in mind, our objective was to perform a meta-analysis of the available data to address the controversy of PEI in patients with UGIB.

Data Search and Screening
A comprehensive electronic literature search of Medline/OVID, PubMed, Scopus, Google Scholar, and Web of Science databases was performed in January 2024.This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement.Search terms included [(endotracheal intubation or intubation or prophylactic) AND (endoscopy or EGD or esophagogastroduodenoscopy) AND (UGIB or gastrointestinal bleeding or upper GI bleeding) AND (adult)].A manual search of the bibliographies of the included articles was performed (JI, MMK, and MLB) to identify any studies that may have been missed during the initial literature search.

Study Selection
Study selection was performed by numerous reviewers (SP, ZIT, IJ, MMK, and MLB).The authors independently screened the abstracts, titles, and full manuscripts to identify the studies eligible for inclusion.English-language studies of adult patients (age >18 years) describing the effect of PEI before EGD in hospitalized GI bleeding patients were included.Outcomes of pneumonia, hospital length of stay, aspiration, and mortality were examined.

Data Extraction
Data was extracted by two independent reviewers (ZT and UF).The authors extracted the following data from identified studies: Study design, cohort characteristics, rate of adverse events of pneumonia, hospital length of stay, aspiration, and mortality.The authors reviewed the extracted data sheet and prepared the final datasheet.

Quality Assessment
We evaluated the quality of included non-randomized studies using the Cochrane Risk of Bias Tool for Nonrandomized Studies (ROBINS-I) [7].Two authors (ZT and UF) conducted the quality assessment separately, and any disagreement was resolved by consensus with a third reviewer (MB).

Statistical Analysis
RevMan 5.4 (Review Manager, Version 5.4, Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012) was utilized for statistical analysis.The authors calculated the mean difference (MD) and corresponding 95% confidence interval (CI) for continuous outcomes and pooled odds ratio (OR) with corresponding 95% CI for dichotomous outcomes.Random effects model was used to calculate the pooled OR with 95% CI and a p-value <0.05 was deemed statistically significant.The I 2 statistics and Cochran's Q test were used for heterogeneity and variance.Publication bias was assessed by funnel plots.

Publication Bias
No significant publication bias was noted by funnel plots (Figure 6).

Quality Assessment
The quality of the studies was assessed using ROBINS-I [7] (  Given the retrospective nature of nearly all studies, significant bias is apparent.Lohse et al. was the only study found to have a low overall risk of bias [3].Overall, the risk of bias was moderate in seven studies [4,5,8,9,[11][12][13] and serious in two studies [2,10].

Discussion
Although endoscopy is a relatively safe procedure, it has been associated with several adverse events, including cardiopulmonary complications such as aspiration and pneumonia.The overall complication rates for EGD range from 0.6 to 5.4 per 1,000, but in cases of UGIB, this can increase to up to 12-22% [15].Some studies have suggested that emergency intubation can lead to complications such as esophageal intubation, development of new pulmonary infiltrates, and even death within 30 minutes of intubation, particularly in hemodynamically unstable patients [16].Emergency endoscopy for UGIB carries a more than 10-fold increase in complication rates (8%) when compared to non-emergency endoscopy (0.7%).Cardiopulmonary complications account for 23-50% of all these adverse events and are responsible for 50-60% of fatalities [5].Aspiration during endoscopy and the resulting aspiration pneumonia have become significant issues, prompting a rise in the utilization of PEI before EGD, even though there is scarce evidence to suggest any improvement in patient outcomes [5].
Previous retrospective studies of PEI in UGIB have shown varying results regarding aspiration, pneumonia, and mortality rates [4,5,12,13].To evaluate these outcomes, a meta-analysis of four studies comparing UGIB patients who received PEI to those who did not was performed in 2015 [6].The meta-analysis demonstrated a significantly higher incidence of pneumonia within 48 hours in the prophylactically intubated group, while trends toward worse outcomes for aspiration and mortality were noted, but were not statistically significant [6].
The common rationale for PEI is airway protection, particularly in the setting of brisk UGIB, where patients are typically intubated for airway protection when the endoscopy is deemed risky to conduct without a secure airway [5,13].However, indications and thresholds for PEI vary among physicians.Studies have indicated that only a minority of gastroenterologists believe that patients with unstable vital signs or ongoing hematemesis should be prophylactically intubated [17].Rehman et al. found similar baseline clinical features between the intubated and non-intubated groups, and the decision to perform endotracheal intubation appeared to have been made subjectively and was largely dependent on the endoscopist's preference [13].Generally, younger patients who are sicker and have massive GI bleed presenting as hematemesis are more likely to undergo PEI [2,11,12].
There also appears to be a temporal trend in the practice of PEI.Its use for EGD has become more prevalent in recent times.Rudolph et al. discovered that in their institution, significantly fewer patients received intubation before EGD in 1988 compared to 1992, even though the overall proportion of intubations during hospitalization remained unchanged [15].Similarly, Koch et al. found that newer faculty were more inclined to the practice of PEI [4].These findings align with data from Tang et al., where most UGIB cases between 2008 and 2013 involved PEI [5].
The suspected etiology of GI bleed also plays a role in the severity and risk of complications, in turn influencing the decision for PEI.Acute variceal hemorrhage (AVH) is known to present with more severe bleeding and a large volume of blood in the upper GI tract.Consequently, AVH poses a high risk of aspiration from emergent EGD which may contribute to cardiopulmonary complications [4,5].This has been reported to occur at a rate of 2.4-3.3%[4].Concurrent hepatic encephalopathy (HE) from decompensated cirrhosis can worsen a patient's ability to protect their airway, increasing the risk of aspiration [5].Perisetti et al. and Hayat et al. indicated that PEI was more commonly performed in patients with cirrhosis or a history of alcohol abuse, who had a higher likelihood of variceal bleeding [2,12].
Of the 11 studies included in our analysis, two [4,5] specifically examined PEI in variceal bleeders (VBs), while Lohse et al. focused only on non-VB cases [3].The remaining studies included both types of bleeders or did not specify [2,[8][9][10][11][12][13]. Tang et al. found no differences in rates of aspiration, pneumonia, and hospital length of stay in prophylactically intubated VBs, but post-EGD intensive care unit stay was longer in this group [5].Koch et al., on the other hand, found higher rates of aspiration events in intubated VBs (19% vs. 0%; p = 0.01) but no significant difference in mortality or hospital length of stay [4].Although both studies only included VBs, there were subtle differences in their inclusion criteria.Koch et al. [4] only included patients with grade 1 HE, while Tang et al. included patients with Grade 1 and 2 HE, the latter of which were more commonly seen in the PEI group (21.5 vs. 8.9%; p = 0.117) [5].In contrast, Lohse et al. included patients undergoing emergent EGD for PUD.Their results indicate that younger patients with more severe presentation and excessive alcohol intake were more likely to undergo PEI.They found increased in-hospital mortality in the PEI group (11.3% vs. 8.5%; p = 0.005), but this was non-significant after adjustment (OR = 1.18; p = 0.188).The length of hospital stay was similar between PEI and no intubation groups (p = 1.108) [3].
Peri-procedural aspiration events remain a common trigger for cardiopulmonary complications seen with EGD and are thus a major reason behind the decision for PEI.A study from Australia that utilized a radiotracer to identify aspiration during routine non-urgent EGD for different indications than UGIB failed to identify any meaningful aspiration, establishing the safety of the procedure [18].However, in the setting of UGIB, an increased risk of cardiopulmonary complications, including aspiration, is often observed.In this regard, studies comparing pre-and post-EGD chest radiographs (CXRs) have shown the development of new infiltrates suggesting intraoperative aspiration events in 14-20% of cases [15].In reality, this could be even higher owing to the lack of sensitivity of CXR in detecting micro-aspiration.Seven studies included in our analysis examined aspiration events in the PEI and no-intubation groups [2,4,5,[10][11][12][13].The results of our meta-analysis do not show a statistically significant improvement in aspiration events with PEI; in fact, it shows a trend toward higher rates of aspiration associated with this practice.However, the results of these studies should be interpreted with caution because, except for one, all are of retrospective design and are thus prone to confounding biases and show considerable heterogeneity as well.
Pneumonia is another concern related to EGD procedures, and it is often considered when deciding on PEI.Seven studies included in our analysis investigated the relationship between PEI and pneumonia rates [2,4,5,[10][11][12][13].Our meta-analysis revealed no statistically significant reduction in pneumonia rates with the use of PEI.However, as with aspiration events, the results should be interpreted cautiously due to the retrospective design of most studies, which can lead to confounding biases and considerable heterogeneity.
The impact of PEI on mortality and hospital length of stay is another important consideration.Some studies in our analysis reported higher mortality in the PEI group [3], while others found no significant difference [4].Our meta-analysis did not show a significant improvement in mortality rates with PEI.Similarly, there was no significant difference in length of stay between the PEI and no-intubation groups.These findings should also be interpreted with caution due to the retrospective design of the studies and the potential for confounding biases and significant heterogeneity.

Conclusions
Our meta-analysis of the available literature on PEI before EGD for UGIB suggests that PEI does not significantly improve patient outcomes in terms of reducing aspiration events, pneumonia rates, mortality, or hospital length of stay.On the contrary, PEI may be associated with higher odds of pneumonia within 48 hours and longer length of stay.However, these findings should be interpreted cautiously due to the retrospective design of most studies and the potential for confounding biases and heterogeneity among them.Further prospective, randomized controlled trials are needed to establish definitive evidence on the use of PEI in the context of EGD for UGIB.

FIGURE 5 :
FIGURE 5: Length of hospital stay.Forest plot demonstrating the comparison of prophylactic intubation versus no intubation for patients with UGIB for the length of hospital stay [2-5,13].UGIB = upper gastrointestinal bleeding; PEI = prophylactic endotracheal intubation