Impact of Continuous Renal Replacement Therapy on Bivalirudin Dosing in Pediatric Extracorporeal Membrane Oxygenation

Abstract

There is an increasing interest in the use of bivalirudin for pediatric extracorporeal membrane oxygenation (ECMO) anticoagulation. However, dosing is not well described in those requiring continuous renal replacement therapy (CRRT). We aimed to determine whether CRRT affects bivalirudin dosing in pediatric ECMO patients. Children ≤18 years of age placed on ECMO and anticoagulated with bivalirudin for ≥24 hours from January 2019 to May 2020 were included. Bivalirudin doses were collected for 144 hours from initiation of bivalirudin or CRRT. Analysis was performed to determine whether CRRT, age, or weight affected bivalirudin dosing. Thirty-one children were included, and 11 (35%) required concomitant CRRT. There was no difference in age (median 9.1 versus 3.2 months, p = 0.15) or days on ECMO (median 11 versus 9, p = 0.7) between those who did or did not receive CRRT. The mean bivalirudin dosing was similar in patients who did or did not require CRRT (median and IQR: 0.13 mg/kg/hour [0.08–0.26] versus 0.15 mg/kg/hour [0.11–0.22], respectively, p = 0.13). Younger age (p < 0.001) and lower weight (p < 0.001) were associated with higher bivalirudin dosing. In our study, bivalirudin dosing did not differ if the patient required CRRT while on ECMO.

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).…”

“…Of note, three studies describing bivalirudin as anticoagulation in the setting of continuous renal replacement therapy (CRRT) or renal impairment reported lower initial and therapeutic bivalirudin doses of 0.1 to 0.3 and 0.1 to 0.6 mg/kg/h, respectively, compared with the patients with normal renal function. 35 38 41 Furthermore, one patient receiving ECMO and plasma exchange required an initial bivalirudin dose of 1.2 mg/kg/h and therapeutic doses of 1.58 to 1.8 mg/kg/h ( Supplementary Material S2 ). 25…”

“…All 28 included studies included baseline characteristics, although 8 studies totaling 220 patients grouped patients by broader age categories, and therefore, a specific age was not provided ( Table 3 ). 35 37 38 39 40 41 42 43 However, it was determined from the studies included that 35% of all patients in this review were less than 1 year of age. Regarding ECMO support and indications, most patients were supported with VA or VV ECMO, and all studies included a total duration of ECMO support.…”

“…There are few studies reporting the dosing requirements of bivalirudin in ECMO and CRRT or renal dysfunction. 35 38 41 Given that bivalirudin is renally eliminated, there is continued need to evaluate the impact of age and renal function on dosing requirements in the setting of renal impairment or renal replacement therapy in the setting of ECMO. Additionally, we found one study reporting higher than normal initial and therapeutic dosing in patients undergoing plasma exchange while on ECMO, indicating a need for additional pharmacokinetic and dosing studies to be conducted in pediatric patients requiring other extracorporeal therapies in addition to ECMO support.…”

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

“…8 Although bivalirudin's halflife is 25 minutes under normal circumstances, approximately 20% of its clearance is provided by the kidneys and as such the half-life increases to up to 4 hours in patients with severe renal impairment. 3,9 Given this increase in half life, dose adjustments e197 in patients with renal impairment was recommended by manufacturer with considerable variability in dose titration having been reported in clinical practice. [5][6][7][10][11][12] Importantly, the optimal dosing and laboratory monitoring for bivalirudin in pediatric ECMO has not been studied.…”