Evidence map›Paper›PMID 36581732›Full record

ArticleClinical pharmacokinetics2023

Low and Highly Variable Exposure to Prophylactic LMWH Nadroparin in Critically Ill Patients: Back to the Drawing Board for Prophylactic Dosing?

Jeroen Diepstraten, Anne van Rongen, Marianne P Zijlstra, Marieke J H A Kruip, Pim L J van der Heiden, Rob Ter Heine

Open access · bronzeAbstract read
In one paragraph

Article in Clinical pharmacokinetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.7field-weighted citation impact, top 30% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 5 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 5 institutions in 1 country.

Jeroen DiepstratenDepartment of Clinical Pharmacy, Amphia Hospital, Molengracht 21, 4818 CK, Breda, The Netherlands. jdiepstraten2@amphia.nl.ORCID http://orcid.org/0000-0002-9437-0533
Anne van RongenDivision of Systems Pharmacology and Pharmacy, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.ORCID http://orcid.org/0000-0003-1023-7514
Marianne P ZijlstraClinical Chemistry Department Reinier, Haga Medisch Diagnostic Centre Delft, Delft, The Netherlands.
Marieke J H A KruipDepartment of Haematology Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0002-0265-4871
Pim L J van der HeidenDepartment of Intensive Care, Reinier de Graaf Hospital, Delft, The Netherlands.
Rob Ter HeineDepartment of Pharmacy, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.ORCID http://orcid.org/0000-0003-2185-8201
Amphia Ziekenhuis · NLErasmus MC · NLLeiden University · NLRadboud University Nijmegen · NLReinier de Graaf Hospital · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectiveLow-molecular-weight heparins are routinely administered to patients in the intensive care unit to prevent venous thromboembolisms. There is considerable evidence that low-molecular-weight heparin doses should be personalised based on anti-Xa levels, but pharmacokinetic data in intensive care unit patients are lacking. This study aimed to characterise the pharmacokinetics and associated variability of the low-molecular-weight heparin nadroparin in critically ill patients.

methodsCritically ill adult patients who were admitted to the intensive care unit and received nadroparin for prophylaxis of venous thromboembolism were included in a study. Population pharmacokinetic analysis was performed by means of parametric non-linear mixed-effects modelling (NONMEM).

resultsA total of 30 patients were enrolled with 12 patients undergoing continuous veno-venous hemodialysis and 18 patients not undergoing continuous veno-venous hemodialysis. Very high variability in pharmacokinetics was observed with an inter-individual variability in the volume of distribution of 63.7% (95% confidence interval 46.5-90.6), clearance of 166% (95% confidence interval 84.7-280) and relative bioavailability of 40.2% (95% confidence interval 29.5-52.6). We found that standard doses of 2850 IE and 5700 IE of nadroparin resulted in sub-prophylactic exposure in critically ill patients.

conclusionsLow exposure and highly variable pharmacokinetics of nadroparin were observed in intensive care unit patients treated with a prophylactic dose. It can be debated whether nadroparin is currently dosed optimally in intensive care unit patients and our findings encourage the investigation of higher and tailored dosing of nadroparin in the critically ill.

Indexed as

NadroparinVenous ThromboembolismAdultAnticoagulantsCritical IllnessHumansAnticoagulantsNadroparin

Identifiers

PMID36581732
PMCPMC9800240
OpenAlexW4313372568

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.