Amanda C Jacques1, Colleen Lougheed2, Erika Macdonald1, Alan Karovitch3, Pierre Giguère4. 1. , BScPharm, ACPR, is a Pharmacist with The Ottawa Hospital, General Campus, Ottawa, Ontario. 2. , BScPhm, ACPR, was, at the time of this study, a Pharmacist with The Ottawa Hospital, General Campus, Ottawa, Ontario. She is now with London Health Sciences Centre, University Hospital, London, Ontario. 3. , MD, FRCPC, MEd, is Head and Chair of the Division of General Internal Medicine, Departments of Medicine and of Obstetrics and Gynecology, as well as a staff physician, The Ottawa Hospital and University of Ottawa, General Campus, Ottawa, Ontario. 4. , BPharm, MSc, is a Clinical Pharmacy Specialist, The Ottawa Hospital and Ottawa Hospital Research Institute, General Campus, Ottawa, Ontario.
Abstract
BACKGROUND: Unfractionated heparin (UFH) administered by IV infusion is effective in preventing myocardial infarction and death after non-ST-elevation acute coronary syndrome. At the authors' centre, preparations of UFH in 0.9% sodium chloride (normal saline; UFH-NS) were used during a shortage of commercially available UFH in dextrose 5% in water (UFH-D5W), the usual preparation. Anecdotal observations raised concerns about the effectiveness of the saline-based preparation in achieving minimally therapeutic anticoagulation. OBJECTIVE: To compare the effectiveness of UFH-NS and UFH-D5W for achieving and maintaining therapeutic anti-factor Xa levels in patients with non-ST-elevation acute coronary syndrome. METHODS: A retrospective cohort study was conducted with 2 groups of 100 consecutive patients who received either UFH-NS or UFH-D5W for a minimum of 24 h after non-ST-elevation acute coronary syndrome in accordance with a weight-based dosing nomogram. RESULTS: A minimally therapeutic level of anti-Xa (≥ 0.31 IU/mL) was achieved within 24 h for 92% of the patients receiving UFH-D5W and 67% of those receiving UFH-NS (absolute risk difference 25%, 95% confidence interval [CI] 13.4%-36.6%; p < 0.001). Infusion of UFH-NS was associated with lower probability of achieving minimally therapeutic anticoagulation (hazard ratio [HR] 2.30, 95% CI 1.68-3.15; p < 0.001) and maintaining therapeutic anticoagulation (HR 2.31, 95% CI 1.69-3.17; p < 0.001) relative to UFH-D5W. Significant differences in the numbers of patients with subtherapeutic and therapeutic anticoagulation, favouring UFH-D5W, were observed at each of the first, second, and third anti-Xa measurements (p < 0.05). Patients receiving UFH-NS required a greater median number of adjustments to the infusion rate during the first 48 h (1.0 v. 0.5 adjustment per day, p < 0.001). There was no difference between groups in terms of major reductions in hemoglobin. CONCLUSIONS: Infusion of UFH-NS was inferior to UFH-D5W for achieving and maintaining therapeutic anticoagulation in patients with non-ST-elevation acute coronary syndrome. Until further study, saline-based heparin infusions should be used with caution, and patients should be monitored closely to ensure timely achievement and maintenance of therapeutic anticoagulation.
BACKGROUND: Unfractionated heparin (UFH) administered by IV infusion is effective in preventing myocardial infarction and death after non-ST-elevation acute coronary syndrome. At the authors' centre, preparations of UFH in 0.9% sodium chloride (normal saline; UFH-NS) were used during a shortage of commercially available UFH in dextrose 5% in water (UFH-D5W), the usual preparation. Anecdotal observations raised concerns about the effectiveness of the saline-based preparation in achieving minimally therapeutic anticoagulation. OBJECTIVE: To compare the effectiveness of UFH-NS and UFH-D5W for achieving and maintaining therapeutic anti-factor Xa levels in patients with non-ST-elevation acute coronary syndrome. METHODS: A retrospective cohort study was conducted with 2 groups of 100 consecutive patients who received either UFH-NS or UFH-D5W for a minimum of 24 h after non-ST-elevation acute coronary syndrome in accordance with a weight-based dosing nomogram. RESULTS: A minimally therapeutic level of anti-Xa (≥ 0.31 IU/mL) was achieved within 24 h for 92% of the patients receiving UFH-D5W and 67% of those receiving UFH-NS (absolute risk difference 25%, 95% confidence interval [CI] 13.4%-36.6%; p < 0.001). Infusion of UFH-NS was associated with lower probability of achieving minimally therapeutic anticoagulation (hazard ratio [HR] 2.30, 95% CI 1.68-3.15; p < 0.001) and maintaining therapeutic anticoagulation (HR 2.31, 95% CI 1.69-3.17; p < 0.001) relative to UFH-D5W. Significant differences in the numbers of patients with subtherapeutic and therapeutic anticoagulation, favouring UFH-D5W, were observed at each of the first, second, and third anti-Xa measurements (p < 0.05). Patients receiving UFH-NS required a greater median number of adjustments to the infusion rate during the first 48 h (1.0 v. 0.5 adjustment per day, p < 0.001). There was no difference between groups in terms of major reductions in hemoglobin. CONCLUSIONS: Infusion of UFH-NS was inferior to UFH-D5W for achieving and maintaining therapeutic anticoagulation in patients with non-ST-elevation acute coronary syndrome. Until further study, saline-based heparin infusions should be used with caution, and patients should be monitored closely to ensure timely achievement and maintenance of therapeutic anticoagulation.
Entities:
Keywords:
acute coronary syndrome; anti-Xa; dextrose; normal saline; unfractionated heparin
Authors: Hani Jneid; Jeffrey L Anderson; R Scott Wright; Cynthia D Adams; Charles R Bridges; Donald E Casey; Steven M Ettinger; Francis M Fesmire; Theodore G Ganiats; A Michael Lincoff; Eric D Peterson; George J Philippides; Pierre Theroux; Nanette K Wenger; James Patrick Zidar Journal: J Am Coll Cardiol Date: 2012-07-16 Impact factor: 24.094
Authors: P Théroux; H Ouimet; J McCans; J G Latour; P Joly; G Lévy; E Pelletier; M Juneau; J Stasiak; P deGuise Journal: N Engl J Med Date: 1988-10-27 Impact factor: 91.245