Cost analysis study comparing the impact of treatment with aprotinin versus tranexamic acid in cardiac surgery under cardiopulmonary bypass.

OBJECTIVES: An increased risk of mortality and postoperative side effects led to aprotinin (Trasylol®) withdrawal from the market in 2008, but since 2018 aprotinin has again been used in France. The French retrospective multicentre APACHE study (AProtinin versus tranexamic Acid in Cardiac surgery patients with High-risk for Excessive bleeding) compared the efficacy of tranexamic acid versus half-dose aprotinin. The aim of this study, ancillary to the APACHE study, is to carry out a medico-economic analysis of the use of these two antifibrinolytics on an APACHE subpopulation. METHODS: Economic data on reimbursement by the French health insurance system were extracted from the program for the data processing of medical information, and quantitative data on the cost of healthcare products were obtained from the hospital pharmacy software. RESULTS: The main analysis of costs for the population shows that the global valuation was not significantly different between the two treatment groups (P=0.60), but the costs of blood products included in the related hospital stay group (Groupe Homogène de séjour [GHS]) (whole blood, platelets and plasma) were higher for the tranexamic acid group (P=0.007). In a sub-analysis of patients alive at discharge, the costs of blood products in addition to GHS (blood-derived medicines) and the costs of blood products in the GHS were higher for the tranexamic acid group (P=0.04 and 0.001, respectively). CONCLUSIONS: The additional cost of aprotinin at the time of purchase is offset by the additional costs of blood products in the tranexamic acid group.

Inter-lung asymmetrical airway closure cause insufflation delay between lungs in acute hypoxemic respiratory failure.

BACKGROUND: Electrical Impedance Tomography (EIT) can quantify ventilation in the two lungs and be used to measure the airway opening pressure (AOP) of each lung. Asymmetrical AOPs can cause inter-lung insufflation delay. OBJECTIVES: To assess the relation between AOP asymmetry and inter-lung insufflation delay at different PEEP levels. METHODS: Patients with acute hypoxemic respiratory failure and airway closure were included. Low-flow pressure-volume curves and EIT signal were recorded during controlled ventilation and for some patients in pressure support ventilation. RESULTS: 23 patients were studied, 22 patients had ARDS, 9 patients had asymmetrical airway closure with an AOP of 10 [6-13] cmH20 in the sicker lung (AOPsicker) vs. 5 [3-9, ] cmH20 in the healthier lung. During a low flow inflation, the inter-lung inflation delay was 0 [0-112]ms vs. 1450 [375-2400]ms in patients without or with asymmetrical AOPs, p < 0.0001. This delay was correlated to the difference of AOP between the 2 lungs, Spearman R2 = 0.800, p < 0.0001. During tidal ventilation, median delay was 0 [0-62] ms vs. 150 [50-355] ms in patients without vs. with asymmetry, p = 0.019. Setting PEEP at the crossing point of a decremental EIT-based PEEP trial decreased the inter-lung insufflation delay. During pressure support insufflation delay could still be measured and was reduced by increasing PEEP from 5 to 10 cmH2O in patient with asymmetrical lung injury. CONCLUSION: In asymmetrical airway closure, titrating PEEP can minimize inter-lung insufflation delay and can be monitored by EIT. Reducing the delay and reducing ventilation asymmetry is also feasible during pressure support ventilation when low flow inflation curves cannot be performed.

Use of Aprotinin versus Tranexamic Acid in Cardiac Surgery Patients with High-Risk for Excessive Bleeding (APACHE) trial: a multicentre retrospective comparative non-randomized historical study.

OBJECTIVES: Following the reintroduction of aprotinin into the European market, the French Society of Cardiovascular and Thoracic Anaesthesiologists recommended its prophylactic use at half-dose for high-risk cardiac surgery patients. We examined whether the use of aprotinin instead of tranexamic acid could significantly reduce severe perioperative bleeding. METHODS: This multicentre, retrospective, historical study included cardiac surgery patients treated with aprotinin or tranexamic acid between December 2017 and September 2020. The primary efficacy end point was the severe or massive perioperative bleeding (class 3-4 of the universal definition of perioperative bleeding). The safety secondary end points included the occurrence of thromboembolic events and all-cause mortality within 30 days after surgery. RESULTS: Among the 693 patients included in the study, 347 received aprotinin and 346 took tranexamic acid. The percentage of patients with severe or massive bleeding was similar in the 2 groups (42.1% vs 43.6%, Adjusted odds ratio [ORadj] = 0.87, 95% confidence interval: 0.62-1.23, P = 0.44), as was the perioperative need for blood products (81.0% vs 83.2%, ORadj = 0.75, 95% confidence interval: 0.48-1.17, P = 0.20). However, the median (Interquartile range) 12 h postoperative blood loss was significantly lower in the aprotinin group (383 ml [241-625] vs 450 ml [290-730], P < 0.01). Compared to tranexamic acid, the intraoperative use of aprotinin was associated with increased risk for thromboembolic events (adjusted Hazard ratio 2.30 [95% Cl: 1.06-5.30]; P = 0.04). CONCLUSIONS: Given the modest reduction in blood loss at the expense of a significant increase in thromboembolic adverse events, aprotinin use in high-risk cardiac surgery patients should be based on a carefully considered benefit-risk assessment.