[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Original Investigation
March 2016

Use of Protamine for Anticoagulation During Carotid EndarterectomyA Meta-analysis

Author Affiliations
  • 1Veterans Affairs Outcomes Group, Department of Veterans Affairs Medical Center, White River Junction, Vermont
  • 2Department of Surgery, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
  • 3The Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, New Hampshire
  • 4The Dartmouth Psychiatric Research Center, Lebanon, New Hampshire
  • 5Section of Vascular Surgery, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
JAMA Surg. 2016;151(3):247-255. doi:10.1001/jamasurg.2015.3592

Importance  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.

Objective  To review the evidence for and against protamine use, both in its association with increased thrombotic complications and with decreased bleeding.

Data Sources  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.

Study Selection  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.

Results  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.