Side Effects of Heparin Lock Solution

Bleeding

Leakage or spillage of the locking fluid from the catheter lumen is a factor with all catheters, but the greatest concern is associated with hemodialysis catheters, in which the instilled heparin may be as many as 5000 units of heparin. In such situations, bleeding from excessive anticoagulation has been reported. This is another reason for the position taken by ASDIN on limiting the heparin lock solution to 1000 units per mL.31

Leakage has been demonstrated to occur immediately following the locking procedure and late during the locked period between uses. Leakage of the locking solution in the late period is associated with gravity; internal compression of the catheter, such as pinch-off syndrome between the clavicle and first rib or the muscle pump action that causes normal venous compression; viscosity of the locking solution; and the number of holes in the catheters. Manufacturers could also have imprecise priming volumes of catheter lumens in specific product literature, thus adding to the volume that spills from the catheter during the locking procedure.

Using the equivalent of a catheter’s priming volume, multiple brands of hemodialysis catheters were filled with 5000 units per mL of heparin. Early leakage was calculated to range between 2900 units and 6550 units of heparin and late leakage was calculated to range between 5350 units and 6850 units. These doses would be enough to cause bleeding in many patients.42

Although leakage from hemodialysis catheters locked with high doses of heparin is known to lead to bleeding episodes, infusion catheters do not produce similar outcomes due to the much lower concentrations of heparin being used. However, leakage of locking solution from any catheter is not a desirable situation. Locking fluid moving out of the catheter lumen is replaced with blood and may increase the risk of lumen occlusion.

Heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT), a severe immunologic drug reaction known to cause arterial and venous thrombosis, raises serious concern regarding the use of heparin. Platelet factor 4 (PF4) is released when platelets are activated, with some PF4 binding to the injected heparin. This combination stimulates the development of immunoglobulin antibodies, known currently as HIT-IgG, whereas older studies used the term “heparin-associated antiplatelet antibodies.”43,44 Platelet counts drop by at least 50% from the baseline value. HIT-IgG activates the clotting cascade, causing formation of thrombosis within 5 to 10 days after heparin exposure begins. Delayed reactions have been reported, with thrombocytopenia and thrombosis occurring as late as 40 days after the heparin has been discontinued.44

The true incidence of HIT caused by heparin lock solution is unknown, but studies have attributed its occurrence to exposure to this small dose of heparin. This indicates that the pathophysiology does not depend on the dose of heparin. A 1999 study reported 3 cases and found 29 previously reported cases in the literature.45 A 2006 study reported that heparin exposure from catheter flushing was the most common cause in 210 of 2046 antibody-positive patients.46 Several other case reports of HIT have associated its occurrence with catheter flushing procedures, and there is 1 report associated with heparin-coated catheters.47-50

A study using argatroban to treat HIT analyzed the multicenter data to identify 23 patients whose only heparin exposure was from catheter flushing procedures. The median heparin dose was 400 units, ranging from 10 to 13,000 units. Catheters were flushed for a mean of 8.1 days, with a range 3 to 16 days, before HIT diagnosis. These authors emphasized that heparin used for catheter flushing may be undocumented in the medical record and therefore may be overlooked as the cause of the problem.51

Those at greatest risk for HIT include those receiving any form of UFH, those receiving treatment with UFH for more than 1 week, surgical patients, and female patients. A scoring system places patients in the moderate-risk group when they are postoperative patients receiving UFH catheter flushes for more than 4 days. This group is estimated to have a risk of 0.1% to 1%. The recommendation for platelet counts in this moderate-risk group is every 2 to 3 days from day 4 to day 14 or until heparin is stopped, whichever is first. This recommendation emphasizes this frequency when practical, realizing that many postoperative patients may be discharged from the hospital prior to the end of this period. Medical patients receiving only heparin lock solution are in the low-risk group, and routine platelet counts are not recommended.44

Medication Errors

The most critical medication errors involving heparin lock solution have resulted in the deaths of at least 3 neonates and put at least 20 others at serious risk for injury. The deaths occurred in an Indiana hospital in 2006 when vials of heparin 10,000 units per mL instead of heparin 10 units per mL were placed in the storage area on the nursing unit. The same error was repeated in California in 2007, although no deaths occurred. In 2008, a medication mixing error in a Texas hospital pharmacy resulted in 17 infants receiving doses of heparin as much as 100 times the intended dose.52

These errors occurred because vials of heparin may have similar appearances, although the dosages are very different. Confirmation bias causes such errors. When nurses look at a label on a vial taken from its customary place, they may see what they anticipate will be on the label rather than what actually is written there.53 They are expecting to see a label of heparin 10 units per mL and do not realize that it actually states heparin 10,000 units per mL.

The Institute for Safe Medication Practices (ISMP) has also received reports of at least 2 deaths and other injury from the mistaken use of insulin instead of heparin to flush central venous catheters.54

Another form of medication error involves the incorrect use of multidose vials. Reports of outbreaks of hepatitis B and C and HIV have been documented as a result of contaminated vials of heparin and normal saline used for catheter flushing. This usually occurs when a contaminated syringe and/or needle is used to withdraw a second dose of solution from the vial. Changing the needle alone is not sufficient to prevent such contamination. Subsequent use of the same vial exposes other patients to this contaminated medication.55-61

The ISMP makes strong recommendations for preventing such errors, including

• standardizing the stock of heparin dosages to a limited number, thus preventing confusion associated with many concentrations;
• separating the storage of heparin and insulin vials in all areas such as countertops, drug carts, and under the laminar flow hood in the pharmacy;
• performing independent double checks by 2 professionals when heparin must be drawn from a vial;
• using bar coding for all medication dispensing and administration; and
• using prefilled syringes for all catheter flushing procedures, preventing the need for syringe preparation by pharmacy or nursing staff.52-54