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Risk factors of active upper gastrointestinal bleeding in patients with COVID-19 infection and the effectiveness of PPI prophylaxis | BMC Gastroenterology


Our present study demonstrated an overall incidence of UGIB in patients with SARS-CoV-2 infection who needed hospitalization of 0.7% (44/6,373 patients). This number was slightly decreased to 0.6% (5/841) after implementing a standard dose of PPI prophylaxis. Importantly, the percentage of patients presenting with active UGIB was reduced from 16 to 0% after prescribing PPI prophylaxis to patients taking steroids and/or anticoagulants. This information supported our first phase data that the absence of PPI prophylaxis was the significant factor associated with active UGIB. In addition, our first phase data showed 26% absolute risk reduction (ARR) when using PPI to prevent active UGIB in patients who admitted with COVID-19 and provided number needed to treat (NNT) of 4. Previous studies had combined data from UGIB and LGIB [2, 6]. To our knowledge, this is the first study that focuses solely on UGIB in COVID-19 patients.

A large retrospective cohort in the United States demonstrated that using antiplatelet or anticoagulant agents was not a risk factor for GI bleeding [2]. Our study supported these findings on the prior use of antiplatelet/anticoagulant and risk of GI bleeding. Patients recently receiving anticoagulant for VTE prophylaxis for COVID-19 infection were also not found to be a risk factor for active UGIB.

The mortality of COVID-19 infected patients with GI bleeding has been previously reported inconclusively [1, 2, 6]. A propensity score-matched case–control study reported that the occurrence of GI bleeding during hospitalization is associated with a significantly increased mortality rate compared to those without GI bleeding with OR 1.58 (95% CI 1.06–2.34, p = 0.02) [2]. A second matched case–control study reported that in-hospital mortality rates were similar between patients with and without GI bleeding [6]. Recently, a meta-analysis study reported no significant association between GI bleeding and overall mortality rate [1]. In our cohort study, we demonstrated no difference in the overall mortality rate of patients with active UGIB group compared to those with inactive UGIB group.

The current guidelines have suggested using PPI as co-therapy in patients requiring anticoagulants only if they had a history of peptic ulcer bleeding [7]. There was no recommendation for prescribing PPI when patients were taking only anticoagulants or corticosteroids without any risk of UGIB. However, we know that patients taking anticoagulant have a risk of bleeding [8]. Two systematic reviews revealed that corticosteroids increased the incidence of GI bleeding, especially in critically ill patients [9, 10]. Thus, we proposed the short-term PPI prophylaxis protocol for patients with COVID-19 infection who received anticoagulants and/or corticosteroids and found it could prevent active UGIB during hospitalization. This may support the future societal guideline on this issue.

This study reported a need for therapeutic endoscopy of 14% for overall GI bleeding and 100% in patients presenting with the clinical of active UGIB. Our data did not differ from previous studies which reported an overall therapeutic endoscopic hemostasis rate between 6–48% [2, 11, 12]. However, no previous study evaluated the need for therapeutic endoscopy in patients with active GI bleeding.

Regarding the Glasgow-Blatchford score (GBS) which is a screening method for determining whether patient with an acute UGIB will likely require endoscopic hemostatic procedure [5]. The performance of the GBS to predict the need for therapeutic intervention and blood transfusion has been widely validated in the previous studies [13, 14]. According to guidelines for UGIB management, it is recommended to perform EGD within the first 24 h after presentation in patients with a GBS of more than 1 [4, 15, 16]. Although the patients in this study had inactive UGIB, they had a median GBS at 10.5. If we had followed the guidelines, we would have had to perform EGD in those patients. This study demonstrated that the threshold for early endoscopy within 24 h in patients with COVID-19 and UGIB should be revised. Those patients could be given more conservative treatment with high-dose PPI and supportive treatment.

A systematic review from the United States showed that 108 of 123 (87.8%) patients with overall GI bleeding were managed conservatively with PPIs, somatostatin analogs, vasopressin analogs, and intravenous fluid resuscitation [17]. Experts from Italy and United States suggest postponing non-urgent endoscopy in those patients [18, 19]. Performing EGD in patients with COVID-19 infection consumes many resources and is costly. The procedure has a high risk of viral shedding which requires a multidisciplinary team, personal protective equipment, and an appropriate negative pressure room. Our study proposed a GBS threshold of 14 or more supported by an excellent AUROC for selecting patients most likely to benefit from urgent EGD.

Our study had certain limitations. First, the number of patients with active upper GI bleeding is limited. Significant testing on mortality rates was likely impacted by the small sample size. Despite the limited sample size, this study was able to demonstrate two significant factors in the multivariable analysis. Second, since our study was a retrospectively design, there were definitely biases which might affect the outcomes, for instance, the incomplete data of tobacco use, alcohol consumption and Helicobacter pylori status. Finally, this study recruited small proportion of patients having an active UGIB in the first phase of study, and this can affect the result of the multivariate regression analysis. This limitation was highlighted by the large 95% CI obtained in the analysis. Nevertheless, this study demonstrated the data from a real-life practice on the emerging disease. A future prospective study on the benefits of PPI for UGIB prevention in patients with emerging viral disease e.g. COVID-19 should be further explored. After incorporating the results of this study with 0.05 alpha and 0.20 beta, the sample size of PPI and non-PPI group in the future prospective randomization study was 36 each.



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