Even with the popularity of off pump coronary artery bypass
grafting (CABG), cardiopulmonary bypass (CPB) is still used in most of the CABG
surgeries throughout the world1. CPB is not possible without
anti-coagulation and the most common method of anti-coagulation for CPB is the
use of heparin (1). Heparin is a
naturally occurring mucopolysaccharide. It combines with antithrombin III (AT
III) and potentiates its effect. (Liu C et al 1987). (2) The half-life of
heparin is approximately 90 minutes and it increases with an increase in plasma
concentration; therefore, it can be considered a concentration dependent drug.
(Rosenberg R et al, 1975). (3)
The Activated anticoagulation test (ACT) is a functional
assay of heparin anticoagulant and is the most widely employed test. The safe
level for conducting CPB is usually 400-480 seconds. ACT level can be
abnormally increased because of patient factors like Hypothermia, haemodilution,
platelet function abnormalities and a decreased fibrinogen level. This can
occur even if there is incomplete heparinization. (Shore-Lesserson et al, 2008). (10)
The most common initial dose of heparin for CPB is 300-400
USP U/kg. Supplemental heparin doses can be given by monitoring of ACT.
(Shore-Lesserson et al, 2006). (5) When the intended ACT cannot be obtained
even with standard heparin dose, the condition is called heparin resistance.
(Jung HJ et al, 2009). (12)
Antithrombin III (AT-III) deficiency, whether congenital or
acquired, is associated with heparin resistance (HR). Other factors leading to
heparin resistance include hemodilution during CPB, prior treatment with
heparin and large quantities of heparin binding protein in the circulation,
which binds to and inactive heparin. (Shore-Lesserson et al, 2006). (15)
For patients undergoing heart surgery, many studies have
reported the incidence of HR to be between 4 and 22%, with the most frequent
causes being AT deficiency, increases in the clearance of heparin the protein
that joins with heparin, and high levels of factor VIII, fibrinogen, and
platelet factor (PF) IV. In addition, HR has also been reported as a result of
using medications such as aprotinin and nitroglycerin. (Ranucci M et al, 2002).
(16) Heparin resistance can lead to administration of additional doses of Heparin
that can later on cause coagulopathy in the intensive care unit (ICU) and
increase the rate of re-exploration for bleeding as well as lead to other adverse
effects such as acute kidney injury. Heparin resistance has not been studied
very well. We studied some of the more important adverse effects in patients
because of heparin resistance.