title: Anti-Xa activity after subcutaneous administration of dalteparin in ICU patients with and without subcutaneous oedema: a pilot study.
abstract: BACKGROUND
  Intensive care unit (ICU) patients often suffer from subcutaneous oedema, due to administration of large fluid volumes and the underlying pathophysiological condition. It is unknown whether the presence of subcutaneous oedema impairs the absorption of dalteparin, a low molecular weight heparin, when it is given by subcutaneous administration for venous thromboembolism prophylaxis. The objective of this study is to compare the anti-Xa activity of dalteparin after subcutaneous administration in ICU patients with and without subcutaneous oedema.
  
  
  METHODS
  This non-randomized open parallel group follow-up pilot study was conducted in two mixed medical-surgical intensive care units at two teaching hospitals. Seven ICU patients with subcutaneous oedema (index group) and seven ICU patients without subcutaneous oedema (reference group) were studied. Anti-Xa activity was determined at 0, 3, 4, 6, 8, 12 and 24 hours after subcutaneous administration of 2,500 IU dalteparin. Plasma concentrations of factor anti-Xa activity were measured using a chromogenic factor Xa inhibition assay.
  
  
  RESULTS
  The characteristics of the index group were: age, 58 years; male/female ratio, 5/2; body mass index at admission, 23.4 kg/m2 (at study day, 30.6 kg/m2). The characteristics of the reference group were: age, 49 years; male/female ratio, 6/1; body mass index at admission, 24.8 kg/m2 (at study day, 25.0 kg/m2). In the index group, creatinine clearance was lower compared to the reference group (71 versus 131 ml/minute, p = 0.003). Sequential organ failure assessment score did not differ between index and reference groups (4 versus 5). Mean arterial pressure was comparable between index and reference groups (91 versus 95 mmHg) and within the normal range. The mean Cmax value was not different between ICU patients with and without subcutaneous oedema (0.15 +/- 0.02 versus 0.14 +/- 0.02 IU/ml, p = 0.34). In the index group, the mean AUC(0-24 h) value was slightly higher compared with the reference group (1.50 +/- 0.31 versus 1.15 +/- 0.25 h.IU/ml, p = 0.31). This difference was not significant.
  
  
  CONCLUSIONS
  In this pilot study, there was no clinically relevant difference in anti-Xa activity after subcutaneous administration of 2,500 IU dalteparin for venous thromboembolism prophylaxis between ICU patients with and without subcutaneous oedema. Critically ill patients seem to have lower anti-Xa activity levels than healthy volunteers.
authors.affiliation: Hospital Pharmacy Midden-Brabant; TweeSteden Hospital and St Elisabeth Hospital, Tilburg, The Netherlands. m.k.rommers@lumc.nl
authors.forename: Mirjam K
authors.initials: MK
authors.lastname: Rommers
authors.forename: Netty
authors.initials: N
authors.lastname: Van der Lely
authors.forename: Toine C G
authors.initials: TC
authors.lastname: Egberts
authors.forename: Patricia M L A
authors.initials: PM
authors.lastname: van den Bemt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000378:metabolism; D017985:Dalteparin / Q000008:administration & dosage* / Q000378:metabolism; D004487:Edema / Q000378:metabolism*; D015951:Factor Xa / Q000378:metabolism; D065427:Factor Xa Inhibitors; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007279:Injections, Subcutaneous; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D015951:Factor Xa; D017985:Dalteparin