Evaluation of Bivalirudin Dosing in Pediatric Extracorporeal Membrane Oxygenation with Renal Insufficiency or Renal Replacement Therapy

Abstract

Bivalirudin offers several important advantages of relevance to the management of extracorporeal membrane oxygenation (ECMO) patients. This multicenter retrospective analysis evaluated the bivalirudin dosing in pediatric ECMO and correlated these doses with the severity of renal dysfunction. A total of 75 patients were included in this analyses: estimated glomerular filtration rate (eGFR) > 60 ml/min/1.73 m2 (n = 29), eGFR 30–60 (n = 18), eGFR < 30 (n = 28), and of those 23 were on renal replacement therapy (RRT). The initial bivalirudin dose used to reach therapeutic anticoagulation in patients with eGFR > 60 was significantly higher than the dose required in those with renal impairment (0.25 mg/kg/hr in patients with eGFR > 60 and 0.19 mg/kg/hr in patients on RRT, 0.18 mg/kg/hr in patients with eGFR 30–60 and 0.13 mg/kg/hr in patients with eGFR < 30 with no RRT). Progressive dose escalations (two to threefold increase) were required to maintain therapeutic range over the initial 4 days of ECMO that coincided with improving renal creatinine clearance during that same time period. Establishing an initial starting dose of bivalirudin contingent upon eGFR is essential for the rapid achievement of target anticoagulation intensity. Further dose adjustments guided by laboratory monitoring is necessary given the dynamic changes in creatinine clearance following ECMO initiation.

Anticoagulation with Intravenous Direct Thrombin Inhibitors in Pediatric Extracorporeal Membrane Oxygenation: A Systematic Review of the Literature

“…The final systematic review was comprised of 28 publications involving 329 patients. There were 14 case reports, [16][17][18][19][20][21][22][23][24][25][26][27][28][29] 13 retrospective cohort studies, [30][31][32][33][34][35][36][37][38][39][40][41][42] and 1 prospective study 43 (►Table 2). All articles were published between 2002 and 2022 (►Supplementary Material S2).…”

“…Among the 28 studies, 22 (totaling 135 patients) reported bleeding rates while receiving IV DTI on ECMO. [17][18][19][20][21][22][23][24][25][26][27][28][29][30]33,[36][37][38][39]42 However, only one study 36 classified bleeding according to standard criteria of major or minor bleeding. 44 The overall weighted average rate of bleeding was 17% and was 8.9%, 33.3% and 0% for those receiving bivalirudin, argatroban, and lepirudin, respectively (►Table 4).…”

“…Of the 28 studies, 21 reported the rates of thrombosis for patients receiving IV DTI, with an overall occurrence of 17%. [16][17][18][19][20][21][22][23][24][25][27][28][29][30][31][36][37][38][39] Thrombosis occurred in 17%, 22% and 0% of patients receiving bivalirudin, argatroban, and lepirudin, respectively (►Table 4). Direct Thrombin Inhibitors Pediatric Extracorporeal Membrane Oxygenation Kiskaddon et al…”

“…Twenty-six of the 28 studies reported overall hospital mortality, [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][35][36][37][38][39][40]42 which was 23%, and 21.3%, 44.4%, and 100% in the bivalirudin, argatroban, and lepirudin groups, respectively (►Table 4).…”

“…Of the 28 studies, 21 reported the rates of thrombosis for patients receiving IV DTI, with an overall occurrence of 17%. 16 17 18 19 20 21 22 23 24 25 27 28 29 30 31 36 37 38 39 Thrombosis occurred in 17%, 22% and 0% of patients receiving bivalirudin, argatroban, and lepirudin, respectively ( Table 4 ).…”