Use of Protamine for Anticoagulation During Carotid Endarterectomy: A Meta-analysis.
OBJECTIVE
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.


METHODS
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.


METHODS
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.


METHODS
Two reviewers extracted data and assessed quality. Random-effects models were used to summarize relative risks (RRs).


METHODS
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; I(2) = 15%; 9 studies), myocardial infarction (RR, 0.89; 95% CI, 0.53-1.51; I(2) = 0%; 3 studies), or mortality (RR, 0.9, 95% CI, 0.62-1.29; I(2) = 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; I(2) = 32%; 10 studies).


CONCLUSIONS
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.
Veterans Affairs Outcomes Group, Department of Veterans Affairs Medical Center, White River Junction, Vermont2Department of Surgery, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire.
Karina A
KA
Newhall
The Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, New Hampshire4The Dartmouth Psychiatric Research Center, Lebanon, New Hampshire.
Elizabeth C
EC
Saunders
Veterans Affairs Outcomes Group, Department of Veterans Affairs Medical Center, White River Junction, Vermont3The Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, New Hampshire.
Robin J
RJ
Larson
Section of Vascular Surgery, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire.
David H
DH
Stone
Veterans Affairs Outcomes Group, Department of Veterans Affairs Medical Center, White River Junction, Vermont3The Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, New Hampshire5Section of Vascular Surgery, Dartmouth Hitchcock Medical.
Philip P
PP
Goodney
D016893:Carotid Stenosis / Q000601:surgery*; D016894:Endarterectomy, Carotid; D006494:Heparin Antagonists / Q000627:therapeutic use; D006801:Humans; D019106:Postoperative Hemorrhage / Q000517:prevention & control*; D011479:Protamines / Q000627:therapeutic use*; D012042:Registries
D006494:Heparin Antagonists; D011479:Protamines