This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kimmel, S. E. Articles by Strom, B. L. Search for Related Content PubMed PubMed Citation Articles by Kimmel, S. E. Articles by Strom, B. L.

CLINICAL STUDIES

Risk factors for clinically important adverse events after protamine administration following cardiopulmonary bypass

Stephen E. Kimmel, MD, MS, FACC^* , Mikkael A. Sekeres, MD, MS^* , Jesse A. Berlin, ScD^*, Norig Ellison, MD, Verdi J. DiSesa, MD^|| and Brian L. Strom, MD, MPH^*

^* Center for Clinical Epidemiology and Biostatistics and Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Cardiovascular Division, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
Department of Anesthesia, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
^|| Division of Cardiothoracic Surgery, Department of Surgery, Allegheny University–East Falls, Philadelphia, Pennsylvania, USA

Manuscript received November 6, 1997; revised manuscript received June 12, 1998, accepted August 20, 1998.

Address for correspondence: Stephen E. Kimmel, MD, MS, University of Pennsylvania School of Medicine, Center for Clinical Epidemiology and Biostatistics, 717 Blockley Hall, 423 Guardian Drive, Philadelphia, Pennsylvania 19104-6021
kimmel{at}cceb.med.upenn.edu

Objectives. The purpose of this study was to determine risk factors for adverse events following protamine administration after cardiopulmonary bypass.

Background. Intravenous protamine administration is associated with a risk of severe systemic reactions. However, risk factors for these events have not been well delineated, thus hampering development of preventive strategies.

Methods. A case–control study nested within a cohort of consecutive patients undergoing surgery requiring cardiopulmonary bypass was performed. The primary case definition included those events (pulmonary hypertensive and systemic hypotensive) occurring within 10 min of protamine administration in the absence of other measurable causes of hemodynamic compromise.

Results. Comparing the 53 cases to the 223 control subjects, three risk factors were independently associated with events (multivariable odds ratio [95% confidence interval]): neutral protamine Hagedorn insulin use (8.18 [2.08, 32.2]); fish allergy (24.5 [1.24, 482.3]), and a history of nonprotamine medication allergy (2.97 [1.25, 7.07]). These risk factors demonstrated an increasingly strong association with progressively more specific case definitions. An estimated 39% of cardiopulmonary bypass patients had one or more of these risk factors. Prior intravenous protamine, central venous pressure prior to protamine, preoperative ejection fraction and the need for inotropes when coming off bypass did not exhibit statistically significant associations with events (all p > 0.15). Prior protamine allergy was associated specifically with an increased risk of pulmonary hypertension (multivariable odds ratio 189; 95% confidence interval 13, 2,856).

Conclusions. Immunologic factors are important in predisposing individuals to protamine reactions, and a substantial proportion of patients are at considerably increased risk. Strategies to reduce the risk of protamine-associated events are needed.

Abbreviations and Acronyms   CI = confidence interval   CPB = cardiopulmonary bypass   CVP = central venous pressure   HUP = Hospital of the University of Pennsylvania   IABP = intra-aortic balloon pump   Ig = immunoglobulin   NPH = neutral protamine Hagedorn   OR = odds ratio

This article has been cited by other articles:

				C Collins and A O'Donnell Does an allergy to fish pre-empt an adverse protamine reaction? A case report and a literature review Perfusion, November 1, 2008; 23(6): 369 - 372. [Abstract] [PDF]

				H. Calkins, J. Brugada, D. L. Packer, R. Cappato, S.-A. Chen, H. J.G. Crijns, R. J. Damiano Jr, D. W. Davies, D. E. Haines, M. Haissaguerre, et al. HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: Recommendations for Personnel, Policy, Procedures and Follow-Up: A report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation Developed in partnership with the European Heart Rhythm Association (EHRA) and the European Cardiac Arrhythmia Society (ECAS); in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), and the Society of Thoracic Surgeons (STS). Endorsed and Approved by the governing bodies of the American College of Cardiology, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, and the Heart Rhythm Society. Europace, June 1, 2007; 9(6): 335 - 379. [Full Text] [PDF]

				U. Krumsdorf, S. Ostermayer, K. Billinger, T. Trepels, E. Zadan, K. Horvath, and H. Sievert Reply J. Am. Coll. Cardiol., October 19, 2004; 44(8): 1714 - 1716. [Full Text] [PDF]

				H. A. Seifert, D. R. Jobes, T. Ten Have, S. E. Kimmel, L. M. Montenegro, J. M. Steven, S. C. Nicolson, and B. L. Strom Adverse Events After Protamine Administration Following Cardiopulmonary Bypass in Infants and Children Anesth. Analg., August 1, 2003; 97(2): 383 - 389. [Abstract] [Full Text] [PDF]

				J. Milot, J. Perron, Y. Lacasse, L. Letourneau, P. C. Cartier, and F. Maltais Incidence and Predictors of ARDS After Cardiac Surgery Chest, March 1, 2001; 119(3): 884 - 888. [Abstract] [Full Text] [PDF]