What is the recommended bivalirudin dosing (loading dose and continuous infusion) and monitoring strategy for an adult on veno‑venous or veno‑arterial extracorporeal membrane oxygenation, including adjustments for renal impairment?

Bivalirudin Dosing for ECMO

Start bivalirudin at 0.02–0.05 mg/kg/hr (without a loading dose) for adults on VV-ECMO or VA-ECMO, targeting an aPTT of 1.5–2 times the normal level, with lower doses (starting at 0.02 mg/kg/hr) for postcardiotomy patients or those with reduced creatinine clearance. 1

Initial Dosing Strategy

• No loading dose is recommended for ECMO patients, unlike the standard percutaneous coronary intervention protocol 1
• Start with continuous infusion at 0.02–0.05 mg/kg/hr for both VV-ECMO and VA-ECMO (excluding postcardiotomy) 1
• This represents a dramatically lower dose than the standard PCI dosing, reflecting the unique pharmacokinetics in critically ill ECMO patients 1

Dose Adjustments for Special Populations

Renal Impairment

• Moderate renal impairment (CrCl 30-59 mL/min): Start at 0.05 mg/kg/hr or lower 2
• Severe renal impairment (CrCl <30 mL/min): Start at 0.05 mg/kg/hr 3, 2
• Bivalirudin clearance is reduced by 45% in moderate renal impairment and 68% in severe renal impairment 3
• Patients on continuous renal replacement therapy (CRRT): Start at 0.07 mg/kg/hr 2
• Patients on intermittent hemodialysis (IHD): Start at 0.07 mg/kg/hr 2
• Patients on sustained low-efficiency daily diafiltration (SLEDD): Start at 0.09 mg/kg/hr 2
• Dialysis patients require higher doses than non-dialyzed patients with similar creatinine clearance due to extracorporeal clearance 2

Postcardiotomy ECMO

• Start at the lower end of the dosing range (0.02 mg/kg/hr) for postcardiotomy VA-ECMO patients 1
• These patients have heightened bleeding risk and may require more conservative anticoagulation 1

Monitoring Strategy

Primary Monitoring

• Use aPTT-based monitoring targeting 1.5–2 times the normal level 1, 4
• This is the same target range used for unfractionated heparin in ECMO 1, 4
• Check aPTT at least daily, and more frequently during dose titration 4

Alternative Monitoring (When aPTT is Unreliable)

• Use diluted thrombin time (TT) if baseline aPTT is abnormal (common in liver failure, post-cardiac surgery, or severe coagulopathy) 1, 4
• Chromogenic anti-IIa testing can be used if institutional protocols exist 1, 4
• Ecarin clotting time (ECT) provides a more linear dose-response relationship 4

Clinical Considerations and Pitfalls

Pharmacokinetic Differences in ECMO

• Bivalirudin has a 25-minute half-life in normal renal function, but this is significantly prolonged in ECMO patients with renal dysfunction 5, 3
• The drug undergoes 80% enzymatic metabolism and only 20% renal excretion, but critical illness alters both pathways 5
• Actual dosing requirements in ECMO are highly variable (range 0.04–0.26 mg/kg/hr in one study, with median 0.15 mg/kg/hr) 6

Dose Escalation with Concurrent CRRT

• Patients on both ECMO and CRRT require 75–125% higher bivalirudin doses compared to ECMO alone 6
• This reflects extracorporeal clearance by the dialysis circuit 6, 7
• One study found median doses of 0.041 mg/kg/hr with hemofiltration versus 0.028 mg/kg/hr without 7

Common Pitfalls

• Do not use standard PCI dosing (0.75 mg/kg bolus + 1.75 mg/kg/hr infusion), as this causes severe bleeding in ECMO patients 1
• Avoid underdosing in dialysis patients—they need higher doses than non-dialyzed patients with similar renal function 2
• Institutional protocols are strongly recommended given the wide dosing variability and lack of standardization 1
• Bleeding complications occurred in 28.6% of patients in one ECMO series, requiring either aPTT goal reduction or temporary holding 6
• Circuit thrombosis requiring component exchange still occurs despite bivalirudin (36% in one series) 6

Efficacy and Safety Data

• Retrospective studies show no difference in bleeding or thrombotic complications between bivalirudin and heparin in ECMO patients 1, 7
• Bivalirudin provides more stable aPTT values with fewer fluctuations >20% compared to heparin (24 vs. 52 episodes, p<0.001) 7
• The drug is particularly useful for heparin-induced thrombocytopenia, heparin resistance, or persistent clotting/bleeding on heparin 6, 7