Calculation Algorithm Reduces Protamine Doses Without Increasing Blood Loss or the Transfusion Rate in Cardiac Surgery: Results of a Randomized Controlled Trial

Kjellberg, Gunilla; Holm, Maja; Fux, Thomas; Lindvall, Gabriella; Linden, Jan van der

doi:10.1053/j.jvca.2018.07.044

Cited by 11 publications

(6 citation statements)

References 24 publications

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“…There are a number of distinctions between our study and this previous work [10]. Notably, Kjellberg and colleagues did not quantitatively measure any coagulation function (other than ACT) as an endpoint, limiting their analysis to bleeding and transfusion.…”

Section: Plos Medicinementioning

confidence: 76%

“…Previous retrospective observational [ 13 , 28 ], prospective observational [ 12 , 29 – 31 ], and pilot randomised controlled trials [ 32 , 33 ] have examined different mathematical models for determining heparin concentration following CPB. Kjellberg and colleagues have performed the sole, adequately powered randomised trial in the literature that compares such a model to a fixed ratio approach [ 10 ]. Like our findings, this study demonstrated a reduction in the amount of protamine required at the conclusion of CPB but did not show a statistically significant difference in blood loss or transfusion.…”

Section: Discussionmentioning

confidence: 99%

“…While small, nonrandomised studies of different models have shown that these approaches may improve coagulation and reduce protamine dose, uptake has been limited by a lack of prospective, randomised data [ 9 ]. To date, only 1 appropriately powered randomised trial has been published [ 10 ], and best practice guidelines continue to recommend the use of fixed dose ratios [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Optimal protamine dosing after cardiopulmonary bypass: The PRODOSE adaptive randomised controlled trial

et al. 2021

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Background The dose of protamine required following cardiopulmonary bypass (CPB) is often determined by the dose of heparin required pre-CPB, expressed as a fixed ratio. Dosing based on mathematical models of heparin clearance is postulated to improve protamine dosing precision and coagulation. We hypothesised that protamine dosing based on a 2-compartment model would improve thromboelastography (TEG) parameters and reduce the dose of protamine administered, relative to a fixed ratio. Methods and findings We undertook a 2-stage, adaptive randomised controlled trial, allocating 228 participants to receive protamine dosed according to a mathematical model of heparin clearance or a fixed ratio of 1 mg of protamine for every 100 IU of heparin required to establish anticoagulation pre-CPB. A planned, blinded interim analysis was undertaken after the recruitment of 50% of the study cohort. Following this, the randomisation ratio was adapted from 1:1 to 1:1.33 to increase recruitment to the superior arm while maintaining study power. At the conclusion of trial recruitment, we had randomised 121 patients to the intervention arm and 107 patients to the control arm. The primary endpoint was kaolin TEG r-time measured 3 minutes after protamine administration at the end of CPB. Secondary endpoints included ratio of kaolin TEG r-time pre-CPB to the same metric following protamine administration, requirement for allogeneic red cell transfusion, intercostal catheter drainage at 4 hours postoperatively, and the requirement for reoperation due to bleeding. The trial was listed on a clinical trial registry (ClinicalTrials.gov Identifier: NCT03532594). Participants were recruited between April 2018 and August 2019. Those in the intervention/model group had a shorter mean kaolin r-time (6.58 [SD 2.50] vs. 8.08 [SD 3.98] minutes; p = 0.0016) post-CPB. The post-protamine thromboelastogram of the model group was closer to pre-CPB parameters (median pre-CPB to post-protamine kaolin r-time ratio 0.96 [IQR 0.78–1.14] vs. 0.75 [IQR 0.57–0.99]; p < 0.001). We found no evidence of a difference in median mediastinal/pleural drainage at 4 hours postoperatively (140 [IQR 75–245] vs. 135 [IQR 94–222] mL; p = 0.85) or requirement (as a binary outcome) for packed red blood cell transfusion at 24 hours postoperatively (19 [15.8%] vs. 14 [13.1%] p = 0.69). Those in the model group had a lower median protamine dose (180 [IQR 160–210] vs. 280 [IQR 250–300] mg; p < 0.001). Important limitations of this study include an unblinded design and lack of generalisability to certain populations deliberately excluded from the study (specifically children, patients with a total body weight >120 kg, and patients requiring therapeutic hypothermia to <28°C). Conclusions Using a mathematical model to guide protamine dosing in patients following CPB improved TEG r-time and reduced the dose administered relative to a fixed ratio. No differences were detected in postoperative mediastinal/pleural drainage or red blood cell transfusion requirement in our cohort of low-risk patients. Trial registration ClinicalTrials.gov Unique identifier NCT03532594.

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Section: Plos Medicinementioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Optimal protamine dosing after cardiopulmonary bypass: The PRODOSE adaptive randomised controlled trial

et al. 2021

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“…This practice has led to a major decrease in the amount of protamine administrated and decreased bleeding and transfusion. 16,61 It is therefore recommended to decrease protamine dosing to a dosing ratio less than 1:1 based on the initial heparin dose to prevent postoperative coagulopathy.…”

Section: Anticoagulation During Cardiopulmonary Bypassmentioning

confidence: 99%

Optimizing Perioperative Blood and Coagulation Management During Cardiac Surgery

Meesters

Heymann

2019

Anesthesiology Clinics

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Major blood loss remains common in cardiac surgery with an incidence of up to 15%. 1,2 Bleeding leads to anemia and blood product transfusion, and can lead to the need for rethoracotomy, which are all independently associated with an adverse outcome (Fig. 1). 3,4 Patient blood management is the bundle of measures to Disclosure Statement: M.I. Meesters does not have any disclosures. C. von Heymann discloses that he has received honoraria for lectures and consultancy work, travel reimbursements and research grants related to the topic of this article from CSL Behring, Novo Nordisk, Ferring GmbH, and Shire over the last 3 years.

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“…Among different products, CM represents a complex mixture of Ad-MSC's secreted products, which is now considered a reasonable and alternative approach in cell therapy. In addition to the previous facts, van Asten's research group reported that the fibroblast growth factor (FGF), isolated in Ad-MSC secretome, exhibited viral replication inhibition properties [11]. The isolation and production of young EV might have an effective therapeutic potential in aging pulmonary injuries [10].…”

Section: Introductionmentioning

confidence: 97%

Mesenchymal stem cell (MSc) secretome: A possible therapeutic strategy for intensive-care COVID-19 patients

2020

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Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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Calculation Algorithm Reduces Protamine Doses Without Increasing Blood Loss or the Transfusion Rate in Cardiac Surgery: Results of a Randomized Controlled Trial

Cited by 11 publications

References 24 publications

Optimal protamine dosing after cardiopulmonary bypass: The PRODOSE adaptive randomised controlled trial

Optimal protamine dosing after cardiopulmonary bypass: The PRODOSE adaptive randomised controlled trial

Optimizing Perioperative Blood and Coagulation Management During Cardiac Surgery

Mesenchymal stem cell (MSc) secretome: A possible therapeutic strategy for intensive-care COVID-19 patients

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