Protamine sulfate can be administered at the conclusion of carotid endarterectomy (CEA) to reverse the anticoagulant effects of heparin and to limit the risk for postoperative bleeding. Protamine use remains controversial owing to concern for increased thrombotic complications with its use.
To review the evidence for and against protamine use, both in its association with increased thrombotic complications and with decreased bleeding.
We searched Medline (1946-2014), EMBASE (1966-2014), Cochrane Library (1972-2014), clinical trial registries (World Health Organization International Clinical Trials Registry and clinicaltrials.gov), and abstracts from conferences of the Society of Vascular Surgery (2002-2014) and American Heart Association Scientific Sessions (1980-2014) in November 2014. No language restrictions were applied.
We included clinical trials and observational studies comparing reversal of heparin with protamine sulfate vs no reversal in patients undergoing carotid revascularization and reporting stroke during hospitalization. Of 360 records screened, 12 studies (3%) of CEA were eligible for data pooling.
Data Extraction and Synthesis
Two reviewers extracted data and assessed quality. Random-effects models were used to summarize relative risks (RRs).
Main Outcome and Measure
Stroke after CEA.
We included 12 observational studies involving 10 621 patients in the meta-analysis. Event rates did not differ significantly between patients who received protamine vs those who did not for the following outcomes: stroke (RR, 0.84; 95% CI, 0.55-1.29; I2 = 15%; 9 studies), myocardial infarction (RR, 0.89; 95% CI, 0.53-1.51; I2 = 0%; 3 studies), or mortality (RR, 0.9, 95% CI, 0.62-1.29; I2 = 0%; 7 studies). The use of protamine was associated with a significant decrease in major bleeding complications requiring reoperation (RR, 0.57; 95% CI, 0.39-0.84; I2 = 32%; 10 studies).
Conclusions and Relevance
Based on available evidence, the use of protamine following CEA is associated with a reduction in bleeding complications, without increasing major thrombotic outcomes, including stroke, myocardial infarction, or death.