Interactive Cardiovascular and Thoracic Surgery 2:424-426(2003)
© 2003 European Association of Cardio-Thoracic Surgery
Best evidence topic - Cardiac general |
In patients post cardiac surgery do high doses of protamine cause increased bleeding?
Kenneth Edward Mclaughlina and
Joel Dunningb,*
a Department of Cardiothoracic Surgery, Wythenshawe, South Moor Road, Manchester, M23 9LT, UK
b Department of Cardiothoracic Surgery, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK
* Corresponding author. Tel.: +44-7801548122
joeldunning{at}doctors.org.uk
Received August 26, 2003;
accepted August 28, 2003
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Abstract
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A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether high doses of protamine causes increased bleeding in patients post cardiac surgery. Altogether 268 papers were found using the reported search, of which five presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these papers are tabulated. We conclude that high doses of protamine can cause increased bleeding and impaired platelet function but these effects have never been demonstrated below a ratio of 2.6:1 protamine to heparin.
Key Words: Evidence-based medicine; Thoracic surgery; Protamines; Haemorrhage
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1. Clinical scenario
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You are called to see a patient who is 1 h post CABG. The patient has bled 300 ml since theatre and the nurse performed an ACT, which was prolonged at 150 s. You know that the heparin had been reversed in theatre using 1.3 mg of protamine to every 1 mg of heparin, and that an additional 25 mg was also given after checking the ACT. You are keen to give another dose of protamine but you have heard that high doses of protamine can cause increased bleeding. You wonder whether this is true, and if so, what levels of protamine would do this?
1.1. Three-part question
In [patients following cardiac surgery] does [high dose protamine] cause [increase bleeding or coagulopathy].
1.2. Search strategy
Medline 1966–July 2003 using the OVID interface [exp thoracic surgery/OR cardiac surgery.mp OR exp cardiac surgical procedures/OR cardiac surgical procedures.mp OR exp cardiopulmonary bypass/OR exp coronary artery bypass/OR CABG.mp] AND [exp protamines/OR protamine.af] AND [exp haemorrhage/OR bleeding.mp OR coagulopathy.mp OR anticoagulation.mp] LIMIT to human studies.
1.3. Search outcome
Two hundred and sixty-eight papers were found of which four were deemed to be relevant. One additional paper was found by checking the reference lists of the four relevant papers [1–5]. The papers are presented in Table 1.
1.4. Clinical bottom line
The studies from Carr et al. and Moshizuki et al. provide convincing evidence that at protamine to heparin ratios above 5:1 platelet aggregation and function does become impaired. In addition, Moshizuki et al. demonstrated that at levels above 2.6:1 the ACT significantly increases.
Interestingly, Butterworth et al. have shown that protamine is eliminated in 20–30 min in physiological situations and Gundry et al. provided evidence that prolonged ACT correlates poorly with the presence of free heparin. An indication of how an ACT based protocol may effect bleeding is given by Jobes et al. who showed that using protamine response tests to govern dosing reduced mediastinal blood loss by 50%.
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2. Conclusion
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High doses of protamine can cause increased bleeding and impaired platelet function, but these effects have never been demonstrated below a ratio of 2.6:1 protamine to heparin.
doi:10.1016/S1569-9293(03)00200-7
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References
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- Butterworth J, Yonggu AL, Prielipp RC, Bennett J, Hammon JW, James RL. Rapid disappearance of protamine in adults undergoing cardiac operation with cardiopulmonary bypass. Ann Thorac Surg. 2002;74:1589–1595[Abstract/Free Full Text]
- Mochizuki T, Olson PJ, Szlam F, Ramsay JG, Levy JH. Protamine reversal of heparin affects platelet aggregation and activated clotting time after cardiopulmonary bypass. Anesth Analg. 1998;87:781–785[Abstract/Free Full Text]
- Jobes DR, Aitken GL, Shaffer GW. Increased accuracy and precision of heparin and protamine dosing reduces blood loss and transfusion in patients undergoing primary cardiac operations. J Thorac Cardiovasc Surg. 1995;110:36–45[Abstract/Free Full Text]
- Carr ME, Carr SL. At high heparin concentrations, protamine concentrations which reverse heparin anticoagulant effects are insufficient to reverse anti-platelet effects. Thrombosis Res. 1994;75:617–630[CrossRef][Medline]
- Gundry SR, Drongowski RA, Klein MD, Coran AG. Postoperative bleeding in cardiovascular surgery. Does heparin rebound really exist? Am Surg. 1989;55:162–165[Medline]
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Top
Abstract
1. Clinical scenario