A 2023 systematic review and meta-analysis analyzed the efficacy of prostacyclin-based anticoagulation strategies in critically ill patients requiring extracorporeal support. The analysis incorporated data from 17 studies, encompassing 1,333 patients, the majority of whom were adults undergoing continuous renal replacement therapy (CRRT), with a smaller subset receiving molecular adsorbent recirculating system therapy. The pooled analysis showed no statistically significant difference in circuit lifespan between the prostacyclin and control groups (mean difference 2.5 hours; 95% confidence interval [CI] -12.0 to 16.9; p= 0.74). However, bleeding events were significantly lower in the prostacyclin-treated cohort (9.5% vs. 17.1%; odds ratio [OR] -1.14; 95% CI -1.91 to -0.37; p<0.001), whereas no significant differences were observed in thrombosis rates (3.6% vs. 2.2%; p= 0.35), hypotension (13.4% vs. 11.0%; p=0.40), or mortality (26.3% vs. 32.7%; p= 0.10). A comprehensive risk-of-bias assessment categorized the included studies as predominantly low to moderate quality, with considerable variability in anticoagulation protocols and prostacyclin dosing. Notably, prostacyclin was administered both as monotherapy and in combination with heparin, and despite this heterogeneity, subgroup analyses reinforced the primary findings. Most studies enrolled adult CRRT patients, limiting the generalizability of results to extracorporeal membrane oxygenation (ECMO) or pediatric populations. Although prostacyclin demonstrated a favorable bleeding profile without increasing thrombotic risk, the lack of significant improvement in circuit lifespan or mortality underscores the need for large-scale, randomized controlled trials to establish its optimal use and efficacy across various extracorporeal modalities. [1]
Several pediatric studies have investigated the use of epoprostenol in maintaining CRRT. A 2024 retrospective cohort study evaluated the efficacy and safety of epoprostenol compared to heparin and citrate anticoagulation in children receiving CRRT. The investigation analyzed medical records from a quaternary care children’s hospital between 2017 and 2022, selecting 101 patients under 18 years of age who exclusively received one of the three anticoagulants during CRRT. Epoprostenol was associated with prolonged circuit longevity compared to heparin and citrate, with a median of 29 hours to first unintended filter change versus 18 and 21 hours, respectively (p= 0.002 and p= 0.003, respectively). Additionally, epoprostenol users required fewer filters per CRRT day (0.53 vs. 0.75 for heparin and 1.0 for citrate; p= 0.001 and p= 0.003, respectively). Safety analyses revealed no significant decline in platelet count over the first seven days of CRRT with epoprostenol, whereas heparin was associated with a significant drop within the first 24 hours (p= 0.020). No differences in VIS were observed between groups, and no CRRT-related bleeding events were documented. A theoretical cost analysis indicated that epoprostenol use was associated with lower daily expenses compared to heparin and citrate. These results suggest that epoprostenol is an effective and cost-efficient anticoagulation strategy for pediatric CRRT, with an advantageous safety profile. [2]
Additionally, a 2024 single-center, retrospective study conducted in the United Kingdom evaluated the use of epoprostenol as the sole anticoagulant in critically ill pediatric patients with liver disease undergoing CRRT. Over a 10-year period, epoprostenol was administered in 96 patients across 353 filter episodes, totaling 18,508 hours of CRRT. The reported median filter lifespan was 48 hours (interquartile range [IQR] 32 to 72), with an effective 60-hour filter survival of 60.5%. Clotting occurred in 22.9% of filters, while 5.9% of filters were associated with major bleeding episodes at a rate of 1.13 per 1,000 hours of CRRT. Additionally, minor bleeding occurred in 5.1% of filters (0.97 per 1,000 hours), and hypotension was observed in 11.6% (2.22 per 1,000 hours). No significant differences were noted in filter lifespan, clotting events, bleeding rates, or transfusion requirements between patients with acute liver failure and those with other liver diseases. Hemodynamic effects were minimal, with no significant drop in mean arterial pressure after one hour of CRRT initiation. Compared to previously reported anticoagulation strategies, epoprostenol maintained comparable circuit longevity with bleeding and hypotension rates similar to those reported for heparin or citrate. [3]
Other relevant studies are available in a limited capacity (e.g., only abstracts). In a 2014 retrospective analysis, the efficacy and safety of epoprostenol used for circuit patency for pediatric patients with acute liver failure on CRRT was assessed. Data were taken over a 4-year period from patients who received epoprostenol 4 ng/kg/min (n= 45) and patients who used unfractionated heparin (n= 26). Median filter life was longer with epoprostenol vs heparin (37.5 h vs 24.5 h; p<0.001). In addition, there was a lower incidence of bleeding episodes with epoprostenol (6.7% vs 34.6%), leading to a significantly lower level of platelet consumption with epoprostenol patients (938 mL vs 1,913 mL). Incidence of hypotension requiring intervention was lower for patients who used epoprostenol (8.9% vs 34%), as well as mortality (31.1% vs 42.3%). As only the abstract is available for scrutiny, these findings should be considered with caution. [4]
Similarly, in a 2006 prospective study, use of epoprostenol in patients requiring maintenance of extrarenal clearance circuits was analyzed versus unfractionated heparin. A total of 389 patients were analyzed, comprising 2,322 filters (66,957 h); of these patients, 54% had a clot. Epoprostenol 4-5 ng/kg/min or unfractionated heparin 5-7 U/kg/h were administered in prefilter perfusion, while patients who used both agents received equal doses of 2.5 U/kg/h. Reduction in blood pressure was observed in two filters following epoprostenol use, which normalized once dose was decreased. Filters anticoagulated with heparin had a lower duration of life vs combined therapy (14 h vs 27 h; p<0.001), with mild bleeding increased in heparin use vs epoprostenol (8% of 1,170 filters vs 3% of 66 filters). Both moderate and serious bleeding were noted in 1% of the heparin-treated filters compared to none with epoprostenol. As the full article is only available in Spanish, caution is warranted in consideration of these findings. [5]
Finally, use of epoprostenol to maintain CRRT patency was presented in a 2023 abstract of a retrospective study (N= 21), in which CRRT filter life up to 96 h following epoprostenol administration was assessed. Median filter life was similar between the pre- and post-epoprostenol groups, though vasopressors were utilized more frequently following epoprostenol administration (norepinephrine-equivalents 0.10 mcg/kg/min vs 0.16 mcg/kg/min; p= 0.003). Though 4 people required blood transfusion <4 units following minor bleeds, no patient required blood transfusions 4 units and above for a major bleed. These findings suggest epoprostenol may have utility in patients unable to receive standard anticoagulation for CRRT. As only the abstract is available for scrutiny, these findings should be considered with caution. [6]