CURRENT EVIDENCE OF PROTAMINE IN CAROTID SURGERY
DOI:
https://doi.org/10.48750/acv.414Keywords:
Protamine, Carotid Surgery, Carotid endarterectomy, Carotid stentingAbstract
Introduction and Objectives: Heparin administration is a standardized step in carotid surgery due to the reduced thromboembolic complication rate during perioperative period. This practice is not free of risks since hemorrhagic complications are associated with a larger number of reinterventions. Historically, protamine, as an agent capable of reverting the anticoagulant effects of heparin has raised controversy due to its association with carotid thrombosis and stroke.
This article aims to review the published literature about the role of protamine reversal in carotid surgery.
Methods: Using Pubmed, 10 articles published from January 2010 until the present date were selected, including two meta-analysis, one systematic review and six large-scale multicentric observational studies. The aim of this study was to identify the risk of myocardial infarction, stroke and death, as well as hemorrhagic complications after the administration of protamine.
Results: Six of the selected articles focused on the effects of protamine during carotid endarterectomy, three on transfemoral carotid stenting and one on transcarotid stenting (TCAR).
All the studies related to patients undergoing carotid endarterectomy where protamine had been administered, showed a statistically significant reduction in bleeding rate with a reduction in the number of patients undergoing surgical reintervention and the number of blood transfusions required. There was no statistical difference in the rate of myocardial infarction, stroke and death. The only study that analyzed the use of protamine on TCAR showed similar results to endarterectomy.
Observational studies showed no differences in the incidence of stroke, myocardial infarction, death and bleeding complications with the use of protamine on transfemoral carotid stenting, yet a systematic review identified protamine as a risk factor for higher 30-day stroke rate.
Patients submitted to surgical reinterventions showed higher rates of stroke, myocardial infarction and death, independently of the administration of protamine.
Conclusion: The scientific data published on the last decade supports the safety of protamine reversal during carotid surgery, lowering hemorrhagic complications without showing an increase in thrombotic events. This is supported by meta-analysis and large-scale observational studies, going against the historical controversy surrounding protamine usage based on small sample analysis and local experience.
Downloads
References
Newhall KA, Saunders EC, Larson RJ, Stone DH, Goodney PP. Use of Protamine for Anticoagulation During Carotid Endarterectomy: A Meta-analysis. JAMA Surg. 2016;151(3):247–255.
Liang P, Motaganahalli R, Swerdlow NJ, Dansey K, Varkevisser RRB, Li C, et al. Protamine use in transfemoral carotid artery stenting is not associated with an increased risk of thromboembolic events. J Vasc Surg. 2021 Jan;73(1):142-150.e4.
McDonald JS, Kallmes DF, Lanzino G, Cloft HJ. Protamine does not increase risk of stroke in patients with elective carotid stenting. Stroke. 2013 Jul;44(7):2028-30.
Applefield D, Krishnan S. Protamine. [Updated 2020 May 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-.
Baracchini C, Ballotta E. The Benefit of Heparin Reversal With Protamine During Carotid Endarterectomy. JAMA Surg. 2016;151(3):255–256.
Boer C, Meesters MI, Veerhoek D, Vonk ABA. Anticoagulant and side-effects of protamine in cardiac surgery: a narrative review. Br J Anaesth. 2018 May;120(5):914-927.
Stone DH, Giles KA, Kubilis P, Suckow BD, Goodney PP, Huber TS, et al. Editor's Choice — Protamine Reduces Serious Bleeding Complications Associated with Carotid Endarterectomy in Asymptomatic Patients without Increasing the Risk of Stroke, Myocardial Infarction, or Death in a Large National Analysis. Eur J Vasc Endovasc Surg. 2020 Dec;60(6):800-807.
Stone DH, Nolan BW, Schanzer A, Goodney PP, Cambria RA, Likosky DS, et al. Vascular Study Group of Northern New England. Protamine reduces bleeding complications associated with carotid endarterectomy without increasing the risk of stroke. J Vasc Surg. 2010 Mar;51(3):559-64, 564.e1.
Patel RB, Beaulieu P, Homa K, Goodney PP, Stanley AC, Cronenwett JL, et al. Vascular Study Group of New England. Shared quality data are associated with increased protamine use and reduced bleeding complications after carotid endarterectomy in the Vascular Study Group of New England. J Vasc Surg. 2013 Dec;58(6):1518-1524.e1.
Mazzalai F, Piatto G, Toniato A, Lorenzetti R, Baracchini C, Ballotta E. Using protamine can significantly reduce the incidence of bleeding complications after carotid endarterectomy without increasing the risk of ischemic cerebral events. World J Surg. 2014 May;38(5):1227-32.
Kakisis JD, Antonopoulos CN, Moulakakis KG, Schneider F, Geroulakos G, Ricco JB. Protamine Reduces Bleeding Complications without Increasing the Risk of Stroke after Carotid Endarterectomy: A Meta-analysis. Eur J Vasc Endovasc Surg. 2016 Sep;52(3):296-307.
Naylor AR, Ricco JB, de Borst GJ, Debus S, de Haro J, Halliday A, et al. Editor's Choice — Management of Atherosclerotic Carotid and Vertebral Artery Disease: 2017 Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg. 2018 Jan;55(1):3-81.
McDonald JS, Kallmes DF, Lanzino G, Cloft HJ. Protamine does not increase risk of stroke in patients with elective carotid stenting. Stroke. 2013 Jul;44(7):2028-30.
Khan M, Qureshi AI. Factors Associated with Increased Rates of Post-procedural Stroke or Death following Carotid Artery Stent Placement: A Systematic Review. J Vasc Interv Neurol. 2014 May;7(1):11-20.
Aronow HD, Gray WA, Ramee SR, Mishkel GJ, Schreiber TJ, Wang H. Predictors of neurological events associated with carotid artery stenting in high-surgical-risk patients: insights from the Cordis Carotid Stent Collaborative. Circ Cardiovasc Interv. 2010 Dec;3(6):577-84.
Liang P, Motaganahalli RL, Malas MB, Wang GJ, Eldrup-Jorgensen J, Cronenwett JL, Nolan BW, Kashyap VS, Schermerhorn ML. Protamine use in transcarotid artery revascularization is associated with lower risk of bleeding complications without higher risk of thromboembolic events. J Vasc Surg. 2020 Dec;72(6):2079-2087.
Schermerhorn ML, Liang P, Eldrup-Jorgensen J, et al. Association of Transcarotid Artery Revascularization vs Transfemoral Carotid Artery Stenting With Stroke or Death Among Patients With Carotid Artery Stenosis. JAMA. 2019;322(23):2313–2322.
