title: Risk factors for clinically important adverse events after protamine administration following cardiopulmonary bypass.
abstract: OBJECTIVE
  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.
authors.affiliation: Center for Clinical Epidemiology and Biostatistics and Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia 19104-6021, USA. kimmel@cceb.med.upenn.edu
authors.forename: S E
authors.initials: SE
authors.lastname: Kimmel
authors.forename: M A
authors.initials: MA
authors.lastname: Sekeres
authors.forename: J A
authors.initials: JA
authors.lastname: Berlin
authors.forename: N
authors.initials: N
authors.lastname: Ellison
authors.forename: V J
authors.initials: VJ
authors.lastname: DiSesa
authors.forename: B L
authors.initials: BL
authors.lastname: Strom
mesh_terms: D002315:Cardiopulmonary Bypass; D016022:Case-Control Studies; D016001:Confidence Intervals; D006439:Hemodynamics; D006494:Heparin Antagonists / Q000009:adverse effects*; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011184:Postoperative Period; D011479:Protamines / Q000009:adverse effects*; D012307:Risk Factors
chemical_list: D006494:Heparin Antagonists; D011479:Protamines