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Heparin stability: effects of diluent, heparin activity, container, and pH.

1980; BMJ; Volume: 33; Issue: 12 Linguagem: Inglês

10.1136/jcp.33.12.1206

1472-4146

K.T. Goodall, C C Chooi, Alexander Gallus,

Chemotherapy-related skin toxicity

The effects have been studied of diluent, heparin activity after dilution, container, and pH on the stability of heparin solutions stored under conditions resembling those present during heparin infusion by intravenous drip or syringe pump.Heparin activity was measured by activated partial thromboplastin time and thrombin clotting time (and, in one set of studies, also by factor Xa inhibitor assay and protamine sulphate neutralisation).Heparin activity was stable for 6 hours regardless of storage conditions.After 24 hours heparin activity was stable when the drug was diluted in 0 9 % saline and stored in plastic, but a small loss of activity was observed in several studies after dilution in 5 % dextrose or storage in glass.A more extensive comparison confirmed a 3-5 % loss in heparin activity over 24 hours after dilution in 5 °/'dextrose.Changing the pH to 3-5 or 10 0 had little effect on storage stability.We conclude that heparin activity in vitro remains stable during short infusions but recommend dilution in 0 9 % saline and a plastic container when a heparin solution is infused over 24 hours.Heparin is now commonly given by continuous intravenous infusion rather than by intermittent injection.For this mode of administration heparin is diluted in one of several intravenous infusion fluids and may then remain at room temperature in the infusion bag, bottle, or syringe for 8-24 hours.It is, therefore, important to know if its anticoagulant activity remains stable in vitro for this time.This question has been repeatedly investigated with varying results (Table ).Thus, it has been re- ported that heparin activity is constant for 24 hours regardless of the diluting fluid or its pH over a wide range,'-4 or that heparin activity is reduced by 40-50% within 1 hour of dilution except in 0-9 00 sodium chloride,5 or that heparin activity is reduced by 50-60% after 4-6 hours in all diluents but then increases again with further storage.6Because of these contradictory and sometimes confusing reports about heparin stability in vitro we decided to re-investigate the question.Further, because there is disagreement about the most appropriate test of heparin effect, we decided to measure heparin stability in vitro using four tests: the