Reoperations for bleeding are cut in half among patients who receive protamine during carotid endarterectomy, a new study has found. That was the main finding revealed by David Stone (Dartmouth-Hitchcock Medical Center, Lebanon, USA) at the 33rd Annual Meeting of the European Society for Vascular Surgery (ESVS 2019; 24–27 September, Hamburg, Germany).
Stone and his team of investigators discovered that protamine administration during the procedure “is an independent predictor of reduced bleeding complications reflected by a 50% reduction in re-operation for bleeding”, he told the audience during a scientific session. “It was not, however, associated with an increased incidence of thrombotic events. The consequences of re-operation for bleeding were not benign but rather associated with substantially higher rates of MI [myocardial infarction], strokes and death.”
Stone identified a need for further research in protamine’s use during carotid endarterectomy in light of ongoing controversy surrounding the practice. “Protamine users will often cite diminished bleeding complications without an attendant increase in thrombotic events while other surgeons remain hesitant to use protamine, noting a perceived increased risk of thrombotic complications,” he said.
The latest research follows a 2010 study conducted by Stone and a team of investigators conducted, which accessed a regional registry in New England, “demonstrating a 50% reduction in significant bleeding events at the time of endarterectomy with protamine use without an increased risk of thrombotic complications”, he said. Furthermore, the researchers believe their work spurred an increase in protamine use across the United States.
For this study, the team widened their scope by using a large national registry to further examine the effect of protamine use during carotid endarterectomy across the country.
“Specifically we sought to determine whether protamine had an impact on serious bleeding complications measured by re-operation for bleeding,” explained Stone. “We also sought to determine whether protamine changed the incidence of thrombotic events, specifically myocardial infarction, stroke and death.”
The investigators identified all carotid endarterectomy procedures performed from 2012-2018, settling on a study cohort of nearly 73,000 operations.
Main outcome measures studied were bleeding requiring re-operation, MI, stroke and death during hospitalisation, Stone said. “Protamine administration was not randomised but determined by individual surgeon preference.”
The results showed variances in protamine use: approximately 70% of US surgeons either routine or rare users, with nearly a third using variably. Similarly, use also differed by region, with some achieving over 90% utilisation while others remained under 50%.
“This variation in protamine use led to nearly a two-thirds to one-third cohort of endarterectomies in which protamine was or was not used, and thus created an excellent study population to address the questions posed in this analysis,” Stone said. “Our main finding is that re-operation for bleeding is reduced by 50% in patients who receive protamine (0.71% vs. 1.43%; p=0.0001).”
He added: “At the same time, we again found no significant difference in the incidence of major thrombotic complications, including MI, stroke and death between protamine-treated and untreated patients.”
Whether or not protamine is administered, Stone said, the consequences of re-operating in the event of bleeding were significant. Such patients demonstrated higher risks of thrombotic events: seven-fold in the case of MI, eight-fold for stroke and a 13-fold higher risk of death.
Stone addressed the study’s limitations. “First, it does not provide Level 1 evidence of a randomised trial but it was sufficiently powered to detect differences in low frequency complications using a real world national experience across the United States,” he said. “Second, the dosing of protamine and heparin was not standardised, which could potentially confound outcomes.”
In sum, Stone said, “we conclude that protamine is a useful adjunct during carotid endarterectomy that reduces major bleeding complications without increasing thrombotic risk. Based on these results and that of our prior work we believe there is now sufficient evidence to support the routine use of protamine during carotid endarterectomy and should be adopted as a benchmark and guideline for carotid surgery.”