In the field of cardiac surgery, managing anticoagulation during and after cardiopulmonary bypass (CPB) is critical for patient safety and surgical success. This study, published in the Journal of Extra-Corporeal Technology in 2025, explores the delicate timing of when to cease cardiotomy suction during the administration of protamine sulfate—a drug used to neutralize heparin at the conclusion of CPB. Conducted by a team from the University of Nebraska Medical Center, this in-vitro investigation is designed to replicate real-world conditions with controlled variables using porcine subjects.
The primary concern addressed in the study is the risk of thrombus formation in the extracorporeal circuit if cardiotomy suction continues while heparin is being reversed. Despite clear guidelines from the American Society for Extracorporeal Technology (AmSECT), clinical practices vary between institutions. Some perfusion teams discontinue suction at the start of protamine administration, while others wait until after a protamine test dose (PTD) or a third of the full dose has been given.
This study sought to determine whether either of these latter approaches compromises the safety of the CPB circuit. The research utilized 60 blood samples drawn from five swine placed on CPB for approximately six hours each. Each sample was analyzed for activated clotting time (ACT) at three checkpoints: post-heparin, after the PTD, and after 1/3 of the full protamine dose. The ACT is a key metric used by perfusionists to assess anticoagulation levels, with values below 480 seconds considered too low for safe bypass.
The findings were compelling. The average ACT decreased from 759.45 seconds post-heparin to 290.35 seconds after the PTD—a 38.2% reduction—and further dropped to 147.53 seconds after 1/3 of the protamine dose, totaling a 50.8% reduction. The statistical significance of both drops was confirmed with p-values less than 0.0001. Additionally, after only the PTD, 95% of ACTs fell below the 480-second safety threshold, and after 1/3 dose, nearly all (96.7%) fell below this level.
The study further reinforced these results by presenting graphical data (see Figure 1 and Figure 2 on pages 3–4). These charts vividly illustrate the nonlinear decrease in ACT as protamine is introduced. Notably, 88.3% of samples were under 300 seconds after 1/3 protamine administration, a value strongly indicative of inadequate anticoagulation for CPB.
What sets this study apart is its in-vitro design using a realistic CPB circuit model. Blood was exposed to the full tubing system, cardiotomy suction components, and the standard drug protocols, simulating actual surgical conditions. This design reduced ethical risks and allowed for controlled examination of timing without patient harm. The use of a pre-calculated protamine dosing algorithm based on heparin concentration and subject weight minimized human error and ensured reproducibility.
Moreover, this research aligns with previous studies, such as those by Jansa et al., which similarly demonstrated the early reversal effect of protamine and the dangers of delayed suction termination. The authors argue that protamine’s impact on ACT is nonlinear and not easily predictable, thus further supporting the strict adherence to established practice guidelines. Continuing suction after PTD or partial protamine administration may seem beneficial for recovering more shed blood, but this benefit comes at a potentially high cost—compromising circuit integrity and patient safety.
Importantly, the study addresses concerns of protamine overdose, which can lead to postoperative bleeding, impaired platelet function, and increased transfusion needs. By limiting protamine exposure in the study design and using micro-dosing into samples instead of full systemic administration, the researchers prevented confounding effects from excess protamine. This precision further validates the results.
The authors conclude that protamine administration must be handled with discipline, and suction should be stopped at the onset of administration, as recommended by AmSECT guidelines. This precaution protects the patient from the risks of thrombosis within the CPB circuit during this vulnerable transitional phase. They urge institutions to standardize this practice and eliminate variability that may jeopardize outcomes.
In summary, this in-vitro study provides strong evidence that even minimal protamine exposure quickly reduces ACT to unsafe levels for CPB. The timing of cardiotomy suction termination is not just a procedural detail—it is a critical decision that affects patient safety and surgical success. With statistical rigor, real-world simulation, and alignment with prior research, this study adds a valuable voice to ongoing efforts for standardization in perfusion practice.
