Anticoagulation Strategies and Filter Life in COVID-19 Patients Receiving Continuous Renal Replacement Therapy

Abstract

Because of the unprecedented increase in critically ill patients with coronavirus disease 2019 (COVID-19), capacity to provide continuous RRT (CRRT) for AKI may quickly be overwhelmed (1). Exacerbating this resource crunch is the hypercoagulability observed in COVID-19 (2,3). Frequent CRRT circuit clotting leads to blood loss and wastage of already overextended resources, and need for troubleshooting increases health care provider exposure to infected patients. At our quaternary care academic institution, we perform CRRT using a uniform protocol in five intensive care units (ICUs). We do not use anticoagulation routinely but add it (mostly heparin) as needed. Additionally, for more than a decade, we have used regional citrate anticoagulation (RCA) as the default protocol in our surgical ICU. During the COVID-19 pandemic, our hospital added ten more ICUs. Systemic anticoagulation was available in all 16 ICUs, whereas RCA remained restricted to the surgical ICU, albeit with less frequent postfilter ionized calcium monitoring to reduce nurse exposure to infected patients. Herein, we describe our experience with the life of 502 CRRT circuits on different anticoagulation regimens in 80 patients with RT-PCR-confirmed COVID-19 who received continuous venovenous hemodialysis (NxStage System One) between March 5 and May 8, 2020 (Figure 1A). These circuits were categorized by their anticoagulation regimen at the time of filter stoppage: heparin (systemic unfractionated or low-mol wt heparin [LMWH]), prefilter heparin, argatroban, RCA (citrate), citrate plus heparin (when patients received systemic heparin for medical indications), or no anticoagulation (none). Circuit clotting was our analysis end point. Circuit life was the time (hours) from initiation of CRRT to clotting or censoring. Circuits that functioned beyond 72 hours were censored at 72 hours. Circuits terminated for reasons other than clotting were censored at the time of termination. We determined the association between circuit clotting and anticoagulation groups by Cox regression in Stata 16 software.

Dialysis Filter Life in COVID-19: Early Lessons from the Pandemic

“…The article describes the filter life of 52 critically ill patients with COVID-19 who required prolonged intermittent RRT via sustained, low-efficiency dialysis compared with a control group of patients without COVID-19 in the same center. Similarly to the study by Shankaranarayanan et al (9), they found that treatment with systemic heparin prolonged the duration of dialysis to 12.3 (interquartile range [IQR], 7.2-24.5) hours compared with 4.5 (IQR, 2.5-9.3) hours with citrate or 4.1 (IQR, 2.5-11.3) hours with no anticoagulation. Compared with patients receiving similar CRRT treatments in the pre-COVID-19 era, filter lives were reduced by 50%, and there was a nine-fold increase in the use of heparin, with a corresponding two-fold increase in bleeding complications.…”

“…The presumption from these data is that systemic hypercoagulability of COVID-19 leads to decreased filter life from clotting, which is supported by high rates of venous thromboembolism in this population, and the use of systemic heparin results in a longer filter life span (9). Hypercoagulability correlates with inflammation during severe COVID-19 and it has been speculated that systemic heparin might decrease thrombosis of large and small arteries, leading to improved clinical outcomes in some patients who are severely ill (11).…”

“…The results of these experiences have recently been published (Table 1) (7-9). Shankaranarayanan et al (9) reported their findings from a quaternary care academic institution in New York, including 80 patients and 502 CRRT circuits. The majority of CRRT treatments were done with anticoagulation (70%), a higher usage rate compared with expectations for patients without COVID-19 (10).…”

“…The authors noted the surprising efficacy of systemic heparin and argatroban relative to regional citrate alone, but also rightfully pointed out the limitations of this retrospective analysis. Patients that were treated with citrate were often those that had a very high thromboembolic risk, and there was an understandably less-rigorous monitoring of postfilter calcium, which could have influenced the efficacy of the delivered dose of citrate (9). Our group at Mass General Brigham similarly found that, across 65 patients treated with continuous venovenous hemofiltration, the use of systemic heparin was associated with longer filter survival (31 versus 7.5 hours, P50.03) and no difference in a small subgroup comparing citrate with no anticoagulation.…”

Successful Use of Argatroban to Treat a Critically Ill Patient with Coagulopathy and Nephropathy Secondary to COVID-19

“…Since our patient's discharge from hospital, a single-center study has suggested argatroban to be effective when utilized as an escalation therapy in patients with COVID-19 who have already developed thromboembolism and who require continuous RRT. 21 Additionally, argatroban use has been described in a small group of patients more profoundly critically ill with SARS-CoV-2 infection, most of whom required extracorporeal membrane oxygenation (ECMO). 22 Aside from RRT and ECMO, an extracorporeal approach to removing circulating SARS-CoV-2 from the bloodstream is also being explored 23 ; effective anticoagulation strategies will be essential if such extracorporeal therapies are to be successful.…”