HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Butterworth, J. Articles by James, R. L. Search for Related Content PubMed PubMed Citation Articles by Butterworth, J. Articles by James, R. L. Related Collections Extracorporeal circulation

Ann Thorac Surg 2002;74:1589-1595
© 2002 The Society of Thoracic Surgeons

---

Original article: cardiovascular

Rapid disappearance of protamine in adults undergoing cardiac operation with cardiopulmonary bypass

^a Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
^b Department of Cardiothoracic Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA

Accepted for publication July 11, 2002.

* Address reprint requests to Dr Butterworth, Department of Anesthesiology, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1009, USA.
e-mail: jbutter{at}wfubmc.edu

BACKGROUND: Despite long use of protamine in cardiac operations, neither protamine concentrations nor pharmacokinetics have been reported in patients.

METHODS: Twenty-eight patients (age, 26 to 80 years) undergoing various cardiac surgical procedures gave their consent to receive 250 mg of protamine sulfate administered intravenously by an infusion pump during 5 minutes. Protamine was administered at the usual intraoperative time after separation from cardiopulmonary bypass for reversal of heparin. Timed arterial blood samples were obtained after protamine infusion. Blood plasma was subjected to solid-phase extraction and high-performance liquid chromatography. Total (free + heparin-bound) protamine concentration versus time data were subjected to pharmacokinetic modeling.

RESULTS: Twenty-six patients completed the study. Total plasma protamine concentrations declined rapidly. Model-independent pharmacokinetic analysis revealed median (range) values as follows: volume of distribution, 5.4 L (0.82 to 34 L); clearance, 1.4 L/min (0.61 to 3.8 L/min); and half-life, 4.5 min (1.9 to 18 min). Schwarz-Bayesian criterion identified a two-compartment exponential model with adjustment for weight in the central compartment volume of distribution as performing better than other compartmental or Michaelis-Menten models.

CONCLUSIONS: Protamine has a very short (approximately 5 minutes) half-life after a single 250-mg dose in adult patients. This short half-life could underlie recurrent anticoagulation after initial apparent reversal of heparin.

This article has been cited by other articles:

				F. Ni Ainle, R. J. S. Preston, P. V. Jenkins, H. J. Nel, J. A. Johnson, O. P. Smith, B. White, P. G. Fallon, and J. S. O'Donnell Protamine sulfate down-regulates thrombin generation by inhibiting factor V activation Blood, August 20, 2009; 114(8): 1658 - 1665. [Abstract] [Full Text] [PDF]

				M. Mittermayr, C. Velik-Salchner, B. Stalzer, J. Margreiter, A. Klingler, W. Streif, D. Fries, and P. Innerhofer Detection of Protamine and Heparin After Termination of Cardiopulmonary Bypass by Thrombelastometry (ROTEM(R)): Results of a Pilot Study Anesth. Analg., March 1, 2009; 108(3): 743 - 750. [Abstract] [Full Text] [PDF]

				J. Dunning, M. Versteegh, A. Fabbri, A. Pavie, P. Kolh, U. Lockowandt, S. A.M. Nashef, and on behalf of the EACTS Audit and Guidelines Commit Guideline on antiplatelet and anticoagulation management in cardiac surgery. Eur. J. Cardiothorac. Surg., July 1, 2008; 34(1): 73 - 92. [Abstract] [Full Text] [PDF]

				A. F. Merry Focus on Thrombin: Alternative Anticoagulants Seminars in Cardiothoracic and Vascular Anesthesia, December 1, 2007; 11(4): 256 - 260. [Abstract] [PDF]

				V. G. Nielsen Protamine enhances fibrinolysis by decreasing clot strength: role of tissue factor-initiated thrombin generation. Ann. Thorac. Surg., May 1, 2006; 81(5): 1720 - 1727. [Abstract] [Full Text] [PDF]

				J. O'Connor, A. Kells, S. Henry, and T. Scalea Vacuum-Assisted Closure for the Treatment of Complex Chest Wounds Ann. Thorac. Surg., April 1, 2005; 79(4): 1196 - 1200. [Abstract] [Full Text] [PDF]

				K. H. T. Teoh, E. Young, M. H. Blackall, R. S. Roberts, and J. Hirsh Can extra protamine eliminate heparin rebound following cardiopulmonary bypass surgery? J. Thorac. Cardiovasc. Surg., August 1, 2004; 128(2): 211 - 219. [Abstract] [Full Text] [PDF]

				A. F. Merry, P. J. Raudkivi, N. G. Middleton, J. M. McDougall, P. Nand, B. P. Mills, B. J. Webber, C. M. Frampton, and H. D. White Bivalirudin versus heparin and protamine in off-pump coronary artery bypass surgery Ann. Thorac. Surg., March 1, 2004; 77(3): 925 - 931. [Abstract] [Full Text] [PDF]

				K. E. Mclaughlin and J. Dunning In patients post cardiac surgery do high doses of protamine cause increased bleeding? Interactive CardioVascular and Thoracic Surgery, December 1, 2003; 2(4): 424 - 426. [Abstract] [Full Text] [PDF]