Prophylactic anticoagulation with enoxaparin: Is the subcutaneous route appropriate in the critically ill?
BACKGROUND
Subcutaneously administered low-molecular-weight heparins are widely used for prevention of venous thromboembolism. The appropriateness of the subcutaneous route in critically ill patients has never been established.


OBJECTIVE
To determine anti-Xa activities in critically ill patients and in noncritically ill patients receiving prophylactic doses of subcutaneous enoxaparin.


METHODS
Prospective, controlled, open-labeled study.


METHODS
Tertiary medical-cardiologic-postoperative intensive care unit and a general medical ward at a university hospital.


METHODS
A total of 16 intensive care unit patients (group 1; age, 61.1 +/- 16 yrs; male/female ratio, 7/9; Acute Physiology and Chronic Health Evaluation II score, 20.9 +/- 7; mechanical ventilation, n = 15; vasopressors, n = 13) and 13 noncritically ill medical patients (group 2; age, 61.7 +/- 9 yrs; male/female ratio, 7/6) were studied. Body mass index (25.7 +/- 5 vs. 24 +/- 6 kg/m2, p = not significant) was comparable and serum creatinine levels (0.83 +/- 0.25 vs. 1.07 +/- 0.3 mg/dL, group 1 vs. 2) were within the normal range in both groups. Patients with impaired renal function, receiving hemofiltration, or requiring therapeutic anticoagulation were not eligible.


METHODS
None.


RESULTS
Anti-Xa activities were determined at 0, 1, 3, 6, and 12 hrs after a single daily subcutaneous dose of 40 mg enoxaparin on day 1 and at 3 hrs after 40 mg of enoxaparin on days 2-5. Mean anti-Xa levels at 0 to 12 hrs were consistently lower in group 1 compared with group 2 by analysis of variance (p =.001 between groups and over time), as was the area under the curve at 0 to 12 hrs (2.6 +/- 1 vs. 4.2 +/- 1.7 units x mL(-1) x hr(-1), group 1 vs. 2, p =.008). Significant differences in anti-Xa activity were also found on days 2-5 (p =.001). Peak anti-Xa activities at 3 hrs after administration were negatively correlated with the body mass index (r = -.41, p <.03). No correlation was found between the anti-Xa activity at 3 hrs and the dose of norepinephrine (r =.12, p =.7).


CONCLUSIONS
Critically ill patients with normal renal function demonstrated significantly lower anti-Xa levels in response to a single daily dose of subcutaneous enoxaparin when compared with medical patients in the normal ward.
Priglinger
U
U
Department of Cardiology, University of Vienna, Austria.
Delle Karth
G
G
Geppert
A
A
Joukhadar
C
C
Graf
S
S
Berger
R
R
Hülsmann
M
M
Spitzauer
S
S
Pabinger
I
I
Heinz
G
G
D000368:Aged; D000704:Analysis of Variance; D000925:Anticoagulants / Q000008:administration & dosage*; D000990:Antithrombin III / Q000378:metabolism*; D015992:Body Mass Index; D003404:Creatinine / Q000097:blood; D016638:Critical Illness; D016903:Drug Monitoring; D017984:Enoxaparin / Q000008:administration & dosage*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011292:Premedication / Q000379:methods* / Q000592:standards; D011446:Prospective Studies; D012307:Risk Factors; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors; D020246:Venous Thrombosis / Q000209:etiology / Q000517:prevention & control*
D000925:Anticoagulants; D017984:Enoxaparin; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D000990:Antithrombin III; D003404:Creatinine