Protamine is the standard drug used to reverse heparin after open-heart surgery involving cardiopulmonary bypass (CPB). A protamine test dose (PTD) is typically administered to assess a patient’s hemodynamic response before full heparin reversal. However, concerns have been raised about PTD’s effect on activated clotting time (ACT) and the potential risk of clot formation in the CPB circuit. This study, conducted at Toronto General Hospital, investigates how PTDs influence ACTs and CPB circuit integrity.
Background and Objective
Cardiac surgeries requiring CPB necessitate the use of heparin for anticoagulation, followed by protamine for reversal. The PTD is given as a precautionary measure to evaluate a patient’s reaction to protamine before administering the full dose. However, previous observations suggested that PTDs might cause a rapid and unpredictable drop in ACT, leading to clot formation in the CPB circuit. This study aimed to analyze the extent of ACT reductions after PTD administration and assess the associated risks.
Methods
A total of 120 patients undergoing cardiac surgery with CPB were included in the study. The procedures included coronary artery bypass grafting (CABG), aortic valve replacements, valve and CABG combinations, and other complex surgeries. ACT values were recorded at multiple stages: before CPB termination, after PTD, and after full-dose protamine administration. The average PTD was 36 ± 21 mg, which constituted approximately 11% ± 7% of the full protamine dose. The ACT values were analyzed using a paired t-test to determine statistical significance.
Results
The study revealed significant variability in ACT reductions following PTD administration. On average, ACT dropped by 40% ± 25% after the PTD, with post-PTD ACTs often falling below the institutional safety standard of 480 seconds for CPB initiation. Specifically, 81% of patients had ACT values below this threshold, and 54% had ACTs below 400 seconds.
Importantly, the ACT response to PTDs was highly unpredictable, with no clear correlation between the PTD amount and the extent of ACT reduction. Some patients experienced minor drops in ACT, while others saw drastic reductions, making it impossible to standardize expectations based on PTD dosage alone.
Discussion and Implications
These findings challenge the assumption that a PTD is too small to significantly impact ACT. The study demonstrated that even small doses of protamine could cause a clinically significant drop in ACT, compromising circuit integrity and increasing clot formation risk. Given this unpredictability, the researchers strongly recommend discontinuing the recovery of mediastinal shed blood into the CPB circuit before administering protamine.
Current practices at many institutions, including Toronto General Hospital, involve keeping CPB suction devices active during PTD administration to conserve blood. However, this study highlights that this approach increases the risk of clot formation, as heparinized patient blood that has been partially reversed by protamine may re-enter the CPB circuit and lead to clotting.
Clinical Recommendations
- Discontinue Mediastinal Shed Blood Recovery Before Protamine Administration – The study supports the American Society for Extracorporeal Technology’s recommendation to stop cardiotomy suction at the onset of protamine administration. This prevents the introduction of partially reversed blood into the CPB circuit, reducing clotting risks.
- Standardize PTD Dosage – Although PTDs varied from 1% to 67% of the full dose in this study, standardizing PTD amounts to a predefined percentage (e.g., 10% of the full dose) and ensuring better communication among the surgical team can improve patient safety.
- Measure ACT After PTD Administration – Given the unpredictable effects of PTDs, checking ACT post-administration can help guide further heparin or protamine adjustments before CPB discontinuation.
- Reevaluate the Necessity of PTDs – Since PTDs do not reliably predict full-dose protamine responses and can lead to ACT drops that threaten circuit integrity, alternative methods for assessing protamine sensitivity should be considered.
Conclusion
This study confirms that PTDs significantly impact ACT in an unpredictable manner, which can jeopardize CPB circuit integrity. The results have led to a shift in clinical practice at Toronto General Hospital, where recovery of mediastinal shed blood is now discontinued before protamine administration. These findings underscore the need for standardized protocols to minimize clotting risks and improve patient outcomes in cardiac surgery.
Study ranking: 4 (high-quality observational study) This study is based on real-world clinical data from 120 patients, providing valuable insights into PTD effects on ACT. While it lacks a randomized controlled trial design, the findings are clinically relevant and have already influenced surgical practices.
