Pharmacological Interventions to Prevent Clotting in Extracorporeal Circuits During Continuous Renal Replacement Therapy

Abstract

What are the risks and benefits of pharmacological interventions to prevent clotting in extracorporeal circuits during continuous renal replacement therapy (CRRT)?Patients who are critically ill in an intensive care unit often develop kidney complications related to multiple factors such as infection, hypotension, and necessary medications. Acute kidney injury occurs in approximately 11% to 18% of hospitalized patients and contributes to an estimated 1.7 million deaths every year.1 Because these patients are hemodynamically unstable, they cannot tolerate standard dialysis, which is typically a 3- to 4-hour procedure. Instead, continuous dialysis is the treatment of choice, and critically ill patients often tolerate it better. This continuous treatment, known as CRRT, provides opportunities for the health care team to introduce treatment modalities that would otherwise cause waste products and fluid to accumulate within the injured kidneys.2Standard practice is to run CRRT continuously for 24 hours; however, the therapy is often inadvertently stopped for periods of time because of clotting in the circuits. When such clotting occurs, the circuits must be changed immediately. The need to change the circuits not only delays treatment but also takes staff time and adds costs. To maintain the full therapeutic effect of CRRT, reducing any interruptions to therapy is essential.2During CRRT, blood contacts the circuit system, which can activate the coagulation pathway. Pharmacological approaches to avoid clotting in CRRT circuits involve several medications including intravenous anticoagulants (eg, unfractionated heparin [UFH], low-molecular-weight heparin, argatroban, citrate), oral anticoagulants (warfarin), and antiplatelet agents.3 The purpose of this systematic review was to assess the benefits and harms of pharmacological interventions for preventing clotting in extracorporeal circuits during CRRT.This systematic review, conducted by Tsujimoto et al,4 included 34 randomized controlled trials (and some quasi-experimental trials) comprising 1960 adult participants. The main primary outcomes investigated included major bleeding, successful prevention of clotting (defined as not needing a circuit change during the first 24 hours), and death from any cause at day 28. The included studies evaluated many different pharmacological comparisons; the most common were heparin derivatives and citrate. Because citrate and UFH are the most commonly used medications to prevent clotting during CRRT,2 this summary describes only the comparison of these 2 interventions.Tsujimoto et al4 independently assessed the risk of bias for each study, including selection, performance, detection, attrition, reporting, and publication biases. They resolved any disagreements by reviewing the data together and through discussion. For dichotomous outcomes, risk ratios (RRs) with 95% CIs were used as measures of treatment effect between various comparisons and outcomes. The authors also used the internationally approved Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to determine the certainty of evidence—high, moderate, low, or very low—for each outcome5: This review showed that, when comparing citrate with UFH to prevent clotting during CRRT, moderate-certainty evidence supports citrate resulting in less major bleeding and having slightly more success at the prevention of clotting.4 The findings from this systematic review align with those of other studies showing that citrate, when compared with UFH, more effectively prolongs the duration of CRRT circuits and reduces the risk of bleeding.6 Currently, several ongoing studies could, once completed or published, be included in similar assessments in future systematic reviews.4The evidence from this systematic review can affect clinical care teams’ decisions when they are creating treatment plans for patients in this population. As nurses caring for critically ill patients, advocating for the best evidence-based treatment remains an important piece of our role. We must always consider the best available evidence and understand the feasibility, appropriateness, meaningfulness, and effectiveness of any intervention to determine whether it is most appropriate to implement in our individual context.