Objective:

The risk of thrombotic complications in critical COVID-19 patients remains extremely high, and multicenter trials failed to prove the survival benefit of escalated doses of low molecular weight heparins (LMWH) in this group. The aim of this study was to develop a pharmacokinetic model of LMWH (nadroparin calcium) according to different stages of COVID-19 severity.

Design:

The investigators performed a prospective observational study.

Patients:

Blood samples were obtained from 43 COVID-19 patients that received nadroparin and were treated with conventional oxygen therapy, mechanical ventilation, and extracorporeal membrane oxygenation.

Setting:

The investigators recorded clinical, biochemical, and hemodynamic variables during 72 hours of treatment. The analyzed data comprised 782 serum nadroparin concentrations and 219 anti-factor Xa levels. The investigators conducted population nonlinear mixed-effects modeling (NONMEM) and performed Monte Carlo simulations of the probability of target attainment (PTA) for reaching 0.2-0.5 IU/ml anti-Xa levels in study groups.

Interventions: None.

Measurements and Main Results:

The investigators successfully developed a one-compartment model to describe the population pharmacokinetics of nadroparin in different stages of COVID-19.

Conclusions:

Different nadroparin dosing is required for patients undergoing mechanical ventilation and ECMO to achieve the same targets as those for non-critically ill patients.

Inclusion Criteria:

• Patients treated in the Department of Anesthesiology and Intensive Care and the Department of Infectious Diseases of a tertiary academic hospital with confirmed SARS-CoV-2 infection with a real-time reverse transcription polymerase chain reaction (RT-PCR) or an antigen test.

Exclusion Criteria:

• Coagulation disorders at the start of the therapy.

First group (Group 1) consisted of 14 patients treated with conventional oxygen therapy only in the infectious diseases department. The second group (Group 2) consisted of 14 mechanically ventilated patients treated in the ICU, and the third group (Group 3) was formed by 15 patients supported with extracorporeal membrane oxygenation (ECMO) and mechanically ventilated in the ICU. The investigators used surviving sepsis campaign guidelines for COVID-19 for the escalation of treatment in the study population.