Heparin Rebound

To minimize the risk of thrombosis on the heart-lung machine, 3-4 mg/kg IV heparin boluses are administered to patients prior to initiating cardiopulmonary bypass. Many institutions also test for adequate heparinization before going on pump using a target activated clotting time (ACT) > 480 seconds. In such large doses, much of the heparin is redistributed across tissues and binding proteins in addition to the “central compartment.” These large doses also extend heparin’s typical, apparent half-life from ~ 30 minutes to > 2 hours.

Heparin anticoagulation is reversed with protamine sulfate (typically in a 1:1 dosage) which has an apparent half-life of ~5 minutes. Logically, protamine will neutralize all of the free fraction of heparin readily accessible in the central compartment, but due to its much shorter half-life, protamine will be cleared before eliminating all of the biologically active heparin gradually liberated from binding proteins. This is the proposed mechanism of heparin rebound.

To mitigate this re-heparinization, many anesthesiologists give 50-100 mg of additional protamine just before chest wiring. The literature also references protamine infusions running for hours post-bypass to continuously neutralize any heparin rebound even outside of the operating room.

Thus far, I have been giving an extra protamine bolus with fascial closure and rechecking an ACT prior to leaving the room. Maybe I’ll change my technique during fellowship. 🙂

The differential for bleeding after cardiopulmonary bypass is incredibly vast. Unidentified surgical bleeding, dilutional coagulopathy, qualitative/quantitative platelet defects, hypothermia, hypocalcemia, and heparin rebound are just some things to consider and correct.

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  1. Thanks for your time Rishi. Did some digging of my own regarding the first question to find out that protamine doses higher than 2,5:1 ratios would be promoting bleeding…. I never do actually a baseline ACT but it is a practice that is good to know.

    Thanks again

  2. Had a dilemma of my own today in a child undergoing an aortopulmonary window closure… I usually give a 1.5:1 ratio. Still the ACT before leaving was 203…. gave a further 500 UI without rechecking though…. With the postoperative bleeding I made another ACT which this time was 370, much higher than the previous one….. Still habe to figure what really happened.
    Have some questions regarding this matter if you don’t mind:
    1- There is a myth among surgeons that if you give more protamine than needed you’d be promoting blleding instead of preventing….. Myth or fact? Still have to debunk that one
    2- There are some special devices which guide the heparin-protamine administration in CPB… HMS if i’m not mistaken…. Do you have any experience using them?
    3- What are the best sites of protamine administration: central catheter or peripheral IV?
    4- Does having heparin in the saline within the pressure infusion cuff interferes with ACT measurement?

    Thanks a lot and sorry for reviving such an old post

    • Sorry for the delayed response man!

      1.) I’ve heard this as well among surgeons. There is some literature citing that excess protamine inhibits factor V and limits the generation of thrombin. There are so many other contributing factors to bleeding after a bypass case (hypothermia, qualitative platelet defects, dilutional coagulopathy, hypocalcemia, etc.) that it’s hard to blame JUST the protamine.
      2.) I’ve heard of nomograms being used (not at any of the hospitals I rotate at) to basically determine the protamine dose for a given ACT.
      3.) I don’t think it matters. I tend to run everything through my central line for peace of mind. I remember reading some study that the incidence of pulmonary vasoconstriction from protamine was not related to the route (peripheral vs central).
      4.) We usually do a baseline ACT before heparinization to go onto cardiopulmonary bypass, so the small amount of heparin in the pressure cuff would be accounted for in that baseline.

      Great questions!


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