Tranexamic Acid in Gastrointestinal Bleeding: A Systematic Review and Meta-Analysis. Dionne JC, Oczkowski S, Hunt BJ, Antonelli M, Wijnberge M, Raasveld SJ, Vlaar AP. Critical Care Med. 2021 Oct 27.
This systematic review and meta-analysis evaluates the literature regarding the use of tranexamic acid (TXA) in patients with gastrointestinal bleeding (GIB). Their primary outcome was mortality at latest follow up. Secondary outcomes included bleeding events (rebleeding, need for surgical intervention, transfusion requirements), arterial thrombotic events (myocardial infarction and stroke), venous thrombotic events (deep vein thrombosis, pulmonary embolism) and incidence of seizure. They broke the studies into two groups: “High dose” (>2g IV TXA in 24hrs) and “Low Dose/Enteral” (≤2g IV TXA/24hrs).
Using the search terms “antifibrinolytic”, “tranexamic acid”, “randomized control trial” and “placebo”, they identified 17,398 articles. After removing duplicates and screening for only those studies involving GIB they included 12 studies for their analysis: a) Five studies used “High Dose” with or without enteral TXA; b) Two studies used “Low Dose” with enteral TXA; c) Five studies used enteral TXA only. Neither High Dose, Low Dose or enteral TXA showed any reduction in mortality. Risk of rebleeding and the need for surgical intervention were not reduced in the high dose group; however, interestingly, risk of rebleeding and the need for surgical intervention were significantly reduced in the low dose/enteral group (7 studies). TXA at either dose did not reduce the number of patients who required red blood cell transfusion. Only one study (HALT-IT) using a high dose TXA strategy recorded the use of plasma and platelets and found no difference in volumes transfused in patients who received TXA vs. those who did not. For arterial thrombotic events, four of the studies utilizing high dose TXA showed no increased risk of stroke, and two studies reported no increased risk of myocardial infarction. There was one study utilizing enteral TXA that reported a single myocardial infarction in the TXA group. Venous thrombotic events were only reported in high dose TXA studies with four showing statistically significant increase in DVT, and five showing statistically increased risk of PE. Seizure risk was only assessed in one trial (HALT-IT) and was significantly increased in patients receiving TXA.
The authors conclude that there is high certainty that high dose IV TXA does not reduce mortality, risk of rebleeding, or need for surgical intervention in patients with GIB. High dose IV TXA did result in a small increase in the risk of seizure and venous thrombotic events. Low dose/enteral TXA did show a small reduction in the risk of rebleeding and need for surgical intervention; however, all studies included in the low dose/enteral group had small sample sizes and therefore certainty cannot be assured. So, while there is a theoretical benefit to control the fibrinolytic activity at the source of bleeding, further study is needed to know if the benefit of enteral/low dose IV TXA outweighs the risk as VTE incidence was not evaluated in these studies. The strength of this paper is the exhaustive systematic review that was performed. The weaknesses are despite multiple studies, the population sizes are still small and there is heterogeneity in TXA administration and dosing making generalization difficult. While more study is warranted, this meta-analysis does signal that locally administered TXA for GI bleed may have benefit over systemic TXA.
Outcomes after extracorporeal membrane oxygenation support in COVID-19 and non-COVID-19 patients.
Kurihara C, Manerikar A, Gao CA, Watanabe S, Kandula V, Klonis A, Hoppner V, Karim A, Saine M, Odell DD, Lung K, Garza-Castillon R, Kim SS, Walter JM, Wunderink RG, Bundinger GRS, Bharat A. Artif Organs. 2021 Oct 25;10.
This is a retrospective cohort study comparing outcomes in patients undergoing VV ECMO for COVID-19 versus non-COVID-19 refractory respiratory failure from January 2015 to September 2020. During the study period 138 patients underwent VV ECMO, 26 of whom had COVID-19 pneumonia. There were some baseline differences between the study groups with BMI and BSA being higher in the COVID-19 group and in the incidence of CKD being higher in the non-COVID-19 group. On initial laboratory findings the COVID-19 group had lower serum creatinine, lower serum albumin, lower INR, and lower PaCO2 but higher serum bicarbonate values versus the non-COVID-19 group. For the complication data, they used a variable called “events per patient day” (EPPD) to normalize events to the number of cannulation days. There was a significantly higher EPPD for both bleeding (0.076 vs. 0.034, p 0.03) and thrombotic complications (0.066 vs. 0.015, p <0.001) in the COVID-19 group vs non-COVID-19 group. Specifically, there were more EPPD in the COVID-19 group for hemothorax (0.020 vs 0.007, p <0.001) and Oral/Nasal Bleeding (0.036 vs. 0.010 events, p 0.04). For thrombotic events, COVID-19 patients had a higher incidence of DVT (0.061 vs 0.011, p<0.001) but no difference in the incidence of PE (0.0 vs. 0.001, p 0.49). Mortality was not significantly different between groups at 30 days, 90 days, 180 days, or 365 days after ECMO initiation. A propensity match was done between twelve COVID-19 patients and twelve non-COVID-19 patients. Mortality was again not found to be different between these two groups. For the entire cohort, Cox multivariable logistic regression found that only total bilirubin predicted post-cannulation mortality (HR 1.08, p<0.001, 1.02-1.14 95% CI). For non-COVID patients, BSA, RESP Score and platelets were independent predictors of post-cannulation survival. For the COVID-19 patients, only INR predicted survival. Additionally, the investigators found that all COVID-19 patients on mechanical ventilation for seven or more days prior to cannulation had 100% mortality. There was no such breakpoint for the non-COVID-19 patients.
The authors conclude that while COVID-19 patients treated with ECMO have a higher rate of both bleeding and thrombotic complications, mortality between the groups was not different. Strengths of this paper include the use of multivariable modeling and propensity matched groups to overcome the discrepancy in the sample sizes. This paper is in line with what has been found in the ELSO registry in many regards, but also shows that at this single center, survival can be accomplished with similar results to non-COVID-19 patients, though often at the expensive of longer ECMO runs and longer hospitalization. Weaknesses of this paper are the lack of explanation for how they performed their propensity matching and also the lack of information about length of stay and the number of cannulation days. The authors state the ECMO runs for COVID-19 patients were longer but provide no data to this effect. Outcome data regarding the use of ECMO in COVID-19 patient is still needed, and more high-quality studies need to be performed.