|Year : 2017 | Volume
| Issue : 3 | Page : 201-209
Prophylactic endotracheal intubation in patients with upper gastrointestinal bleeding undergoing endoscopy: A systematic review and meta-analysis
Fayez Alshamsi1, Roman Jaeschke2, Bandar Baw3, Waleed Alhazzani2
1 Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates
2 Department of Medicine, McMaster University, Hamilton; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada
3 Division of Emergency Medicine, McMaster University, Hamilton, Canada
|Date of Web Publication||21-Aug-2017|
Department of Medicine, Division of Critical Care St Joseph's Healthcare, McMaster University, 50 Charlton Avenue, Postal Code L8N 4A6, Hamilton, Ontario
Background: Patients with upper gastrointestinal bleeding (UGIB) often require urgent or emergent esophagogastroduodenoscopy (EGD) and are at risk of complications such as aspiration of gastric content or blood. The role of prophylactic endotracheal intubation (PEI) in the absence of usual respiratory status-related indications is not well established.
Methods: We searched Medline, EMBASE, Cochrane Library's Central Register of Controlled Trials (CENTRAL) and SCOPUS from inception through July 2017 without date or language of publication restriction. We included studies that compared PEI with usual care (UC) in patients with acute UGIB, and reported any of the following outcomes: aspiration, pneumonia, mortality and length of stay. We excluded studies in which majority of included patients required intubation due to respiratory failure or decreased level of consciousness. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence for each outcome.
Results: We did not identify any randomized trials on this topic. We included 10 observational studies (n = 6068). We were not able to perform any adjusted analyses. PEI was associated with a significant increase in aspiration (OR 3.85, 95% CI, 1.46, 10.25; P = 0.01; I2 = 56%; low-quality evidence), pneumonia (OR 4.17, 95% CI, 1.82, 9.57; P = 0.0007; I2 =52%; low-quality evidence) and hospital length of stay (mean difference 0.86 days, 95% CI 0.13, 1.59; P = 0.02; I2 = 0; low-quality evidence), without clear effect on mortality (OR 1.92, 95% CI, 0.71, 5.23; P = 0.2; I2 = 95%; very low-quality evidence).
Conclusions: Low- to very low-quality evidence from observational studies suggests that PEI in the setting of UGIB may be associated with higher rates of respiratory complications and, less likely, with increased mortality. Although the results are alarming, the lack of higher quality evidence calls for randomized trials to inform practice.
Keywords: Endoscopy, systematic review, meta-analysis, prophylactic endotracheal intubation, upper gastrointestinal bleeding
|How to cite this article:|
Alshamsi F, Jaeschke R, Baw B, Alhazzani W. Prophylactic endotracheal intubation in patients with upper gastrointestinal bleeding undergoing endoscopy: A systematic review and meta-analysis. Saudi J Med Med Sci 2017;5:201-9
|How to cite this URL:|
Alshamsi F, Jaeschke R, Baw B, Alhazzani W. Prophylactic endotracheal intubation in patients with upper gastrointestinal bleeding undergoing endoscopy: A systematic review and meta-analysis. Saudi J Med Med Sci [serial online] 2017 [cited 2017 Nov 22];5:201-9. Available from: http://www.sjmms.net/text.asp?2017/5/3/201/213317
| Introduction|| |
Upper gastrointestinal bleeding (UGIB) can result in significant morbidity and mortality. The mainstay treatment is endoscopic therapy whenever possible. As opposed to elective esophagogastroduodenoscopies (EGD), EGDs performed in emergency or critical care setting, especially in the presence of significant hematemesis, can be associated with significant cardiac and respiratory compromise. Therefore, it is not uncommon to perform prophylactic endotracheal intubation (PEI) in such patients to prevent aspiration or to assure that a agitated or confused patient is not actively resisting the procedure.
While it is possible that endotracheal intubation is beneficial for patients with UGIB and concomitantly decreased level of consciousness, agitation or hypoxia, the value of endotracheal intubation in patients with large hematemesis and no other indication for intubation is less clear. The recent European guidelines issued a weak recommendation to perform endotracheal intubation in patients with encephalopathy or agitation, while other guidelines did not address this issue.,, The issue of performing PEI in patients without the above-mentioned characteristics was not addressed. A survey conducted over a decade ago demonstrated a considerable variation in the believes and practices of gastroenterologists with regards to endotracheal intubation in the presence of UGIB. Due to the complexity of this topic and the lack of clear guidance, we undertook a systematic review to determine the effect of prophylactic intubation on patient-important outcomes in the context of UGIB.
| Methods|| |
Studies were eligible if (1) the study design was a randomized controlled trial (RCT) or, if not available, an observational design; (2) the study included patients with UGIB requiring emergent esophagogastroduodenoscopy (EGD); (3) patients underwent PEI (intubation done preemptively to protect the airways in the absence of other indications for intubation) and the control group included patient who did not undergo endotracheal intubation; (4) the study reported any of the following outcomes: aspiration (as defined by authors of those studies), pneumonia (as defined by authors of those studies), mortality and hospital length of stay.
We searched Medline, EMBASE, Cochrane Library's Central Register of Controlled Trials (CENTRAL) and SCOPUS from inception through July 2017. Our search strategy is detailed in Supplementary Appendix I [online only] [Additional file 1]. We did not apply any language or date of publication restrictions. Two reviewers, in duplicate, screened the titles and abstracts for potentially eligible articles. The reviewers then assessed the full text of the articles for final eligibility. We also screened references of relevant articles to identify additional studies not captured in database searches. Disagreement between reviewers was resolved by consensus and a third reviewer was consulted in cases it was not achieved.
Two reviewers independently extracted data from eligible studies using standard data abstractions forms. We resolved disagreements by discussion and consensus.
Risk of bias assessment
Two reviewers independently assessed the risk of bias. We used the Newcastle-Ottawa Scale (NOS) to assess the risk of bias for non-randomized studies. Using this scale, studies are judged based on the following three domains: selection of the study groups [maximum 4 stars (points)]; comparability of the groups (maximum 2 points) and ascertainment of the outcome of interest (maximum 3 points), yielding a maximum possible score of 9 [Supplementary Appendix II, online only] [Additional file 2].
We used Revman software (Review Manager, version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014) for data analysis. We used a random-effects model, as described by Dersimonian and Laird, to pool weighted effects of estimates across all studies. Study weights were estimated using the inverse variance method. We calculated pooled odds ratios (OR) and mean differences (MD) for dichotomous and continuous outcomes, respectively, with corresponding 95% confidence intervals (CI). Statistical heterogeneity was assessed using Chi-square and I2 statistics, with significant heterogeneity defined as P < 0.10 or I2 > 50%. We planned to conduct a meta-analysis of adjusted effect estimates, if reported, to generate pooled adjusted OR with 95% CI.
We performed one subgroup analysis by type of bleeding (variceal versus other) hypothesizing that variceal bleeding is associated with larger benefit from intubation.
We performed sensitivity analysis excluding studies published in abstract form only,,, and excluding the abstract by Lee et al., as the data overlapped with their full-text publication on a later date. 13 Finally, we performed a post hoc analysis excluding the study by Rudolph et al. due to lack of clarity in the reporting outcomes of the study groups.
We planned to inspect funnel plots and to use Egger's test to assess for publication bias for outcomes that included ≥10 studies.
Quality of evidence
We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to assess the quality of evidence for each outcome.
| Results|| |
Characteristics of included studies
Our initial search identified a total of 601 citations. After eliminating duplicates, 500 citations remained, of which 489 were non-relevant. Eleven ,,,,,,,,,, articles were retrieved for full-text assessment. Of those, we excluded an abstract  that was subsequently published as a full text [Figure 1]. We did not identify any randomized trials. A total of 10,,,,,,,,, retrospective observational studies (7 full-text articles ,,,,,, and 3 abstracts ,,) enrolling 6068 patients met our eligibility criteria. Two studies exclusively enrolled patients with variceal bleeding., Characteristics of included studies are presented in [Table 1].
Risk of bias assessment
Two reviewers assessed the risk of bias using NOS, and its assessments are presented in [Table 2].
Six studies ,,,,, enrolling 620 patients reported on incidence of aspiration [Figure 2]. Conventional analysis showed that PEI was associated with a significant increase in probability of aspiration (OR 3.85, 95% CI, 1.46, 10.25; P = 0.01; I2 = 56%; low-quality evidence).
Five studies ,,,, enrolling 1912 patients reported on incidence of pneumonia [Figure 3]. PEI was associated with a significant increase in probability of developing pneumonia (OR 4.17, 95% CI, 1.82, 9.57; P = 0.0007; I2 =52%; low-quality evidence).
Eight studies ,,,,,,, enrolling 5818 patients reported on mortality [Figure 4]. PEI did not affect mortality to a statistically significant degree (OR 1.92, 95% CI, 0.71, 5.23; P = 0.2; I2 =95%; very low-quality evidence).
Hospital length of stay
Six studies ,,,,, enrolling 4188 patients reported on length of stay in hospital [Figure 5]. PEI was associated with a small but statistically significant increase in length of stay (MD 0.86 days, 95% CI 0.13, 1.59; P = 0.02; I2 = 0; low-quality evidence).
We conducted one subgroup analysis by type of bleeding; two studies (n = 172) included only patients with variceal bleeding., We did not detect any significant subgroup differences across all outcomes. Details of the results of subgroup analysis are presented in [Supplementary Figure I] [Additional file 3], [Supplementary Figure II] [Additional file 4], [Supplementary Figure III] [Additional file 5], [Supplementary Figure IV] [Additional file 6] [online only].
Sensitivity analysis, excluding three studies published in the abstract form (n = 1768),,, yielded similar results for pneumonia, mortality and length of stay outcomes. However, for aspiration outcome, the results were no longer statistically significant (OR 4.39, 95% CI 0.75, 25.66; P = 0.1; I2 = 77%). Our second sensitivity analysis, excluding the Lee et al. abstract, did not significantly alter the effect on mortality (OR 2.3, 95% CI 0.79, 6.99; P = 0.12; I2 = 96). We present the details of sensitivity analyses in [Supplementary Figure V] [Additional file 7], [Supplementary Figure VI] [Additional file 8], [Supplementary Figure VII] [Additional file 9], [Supplementary Figure VIII] [Additional file 10], [Supplementary Figure IX] [Additional file 11], [Supplementary Figure X] [Additional file 12] [online only].
Fewer than 10 studies were included for individual outcomes; therefore, we were not able to assess for publication bias.
Quality of evidence
The quality of evidence using the GRADE system ranged between very low to low across study outcomes, mainly due to observational nature of data and the lack of adjustment for important confounders (risk of bias), and also due to inconsistency and imprecision. The large intervention effect was offset by these limitations. The details of quality assessment are presented in [Table 3].
| Discussion|| |
In this systematic review, we identified 10 observational studies (6068 patients) that reported the effect of endotracheal intubation on clinical outcomes of patients with UGIB undergoing endoscopy. Low-quality evidence suggest that PEI is associated with a higher probability of developing pneumonia and aspiration, longer stay in the hospital, and less likely and statistically non-significant impact on mortality.
A recent meta-analysis of four observational studies (n = 367) showed a significant increase in pneumonia within 48 hours of endoscopy in a group of patients undergoing PEI, without affecting the risks of death or aspiration. Our meta-analysis included more studies and patients (10, n = 6068), potentially improving the precision of our findings. We did not apply any restrictions on date or language of publication. In addition, we used the GRADE approach to assess the quality of the evidence, and adhered to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) reporting guidelines.
Although the results of this meta-analysis are intriguing, it needs to be interpreted with great caution. Observational studies tend to be at risk of yielding biased results, study groups differ often in prognosis (i.e. confounders). Even when adjustment for important variables is possible, it may not be enough to yield reliable results. In our meta-analysis, we used only un-adjusted (crude) values, as almost all studies did not report adjusted estimates. This is an important limitation of the results, as it is challenging to determine whether the observed effects are true or confounded. It appears intuitive that the more unstable the patient is (i.e., with more bleeding and vomiting, hypoxic, agitated, non-cooperative, aspirating or judged at higher risk of aspiration), the more likely intubation is performed. Because of the observational nature of studies, lack of adjustment for the severity of clinical situation as well as additional inconsistency among study results and imprecision of estimates, the quality of the results is judged as very low to low. This markedly limits our confidence that the observed effects are true. Therefore, over-interpretation of the results should be avoided and we believe that these results, although alarming, should be considered as hypothesis generating. At the same time, these results should alert clinicians to the fact that PEI may be associated with harm, and that decision-making should take into consideration this possibility. The information we have found, including lack of higher quality data, also indicates the need for a proper randomized trial to be performed in this population of patients.
| Conclusion|| |
Low to very low- quality evidence suggest that PEI may be associated with higher risk of respiratory complications. Future randomized trials or, if not possible, prospectively matched cohort studies are needed to confirm or dispute these findings.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3]