title: Hypersensitivity reactions to aprotinin re-exposure in paediatric surgery.
abstract: OBJECTIVE
  Hypersensitivity to aprotinin is low (1-3%) but more likely with re-exposure. The manufacturer issued a black box warning which lists aprotinin re-exposure within 1 year of prior exposure as a contraindication. We investigated the temporal relationship between re-exposure interval and hypersensitivity in children.
  
  
  METHODS
  With Human Research Review Board approval, charts of all patients exposed to aprotinin during cardiac surgery were reviewed. We extracted data for re-exposure interval and hypersensitivity to skin tests, intravenous test dosing or infusion of the loading dose. We defined systemic hypersensitivity as haemodynamic instability, respiratory symptoms or diffuse skin reaction temporally related to exposure.
  
  
  RESULTS
  From March 1994 to June 2007, there were a total of 2333 aprotinin exposures in 1824 patients. A total of 509 re-exposures occurred in 381 patients: 280 in 244 patients with early (within 1 year) re-exposure and 229 in 222 patients with late (after 1 year) re-exposure. Thirteen systemic hypersensitivity reactions occurred in the 509 re-exposures (2.6%): two during skin testing and 11 during the loading dose. Although the incidence of local hypersensitivity was increased with early re-exposure (6/280 or 2.1% vs 0/229, p=0.019), the incidence of the systemic reaction was not different between early and late re-exposures (6/280 or 2.1% (CI 0.8-4.6%) vs 7/229 or 3.1% (CI 1.2-6.2%), p=0.6). Six patients with a previous hypersensitivity reaction had an additional re-exposure to aprotinin; one of these patients had a systemic reaction during the third exposure.
  
  
  CONCLUSIONS
  The incidence and type of hypersensitivity to aprotinin re-exposure in our cohort is consistent with previous reports. Repeat exposure within 1 year did not increase the risk of systemic hypersensitivity.
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Herma Heart Center at the Children's Hospital of Wisconsin, Milwaukee, WI, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Siehr
authors.forename: Eckehard
authors.initials: E
authors.lastname: Stuth
authors.forename: James
authors.initials: J
authors.lastname: Tweddell
authors.forename: George
authors.initials: G
authors.lastname: Hoffman
authors.forename: Todd
authors.initials: T
authors.lastname: Troshynski
authors.forename: Deborah
authors.initials: D
authors.lastname: Jones
authors.forename: Michael
authors.initials: M
authors.lastname: Mitchell
authors.forename: Nancy
authors.initials: N
authors.lastname: Ghanayem
mesh_terms: D000293:Adolescent; D000328:Adult; D007611:Aprotinin / Q000008:administration & dosage / Q000009:adverse effects*; D006348:Cardiac Surgical Procedures; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D003875:Drug Eruptions / Q000209:etiology; D004342:Drug Hypersensitivity / Q000209:etiology*; D004812:Epidemiologic Methods; D006490:Hemostatics / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007430:Intraoperative Care / Q000009:adverse effects / Q000379:methods; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D012882:Skin Tests; D013997:Time Factors; D055815:Young Adult
chemical_list: D006490:Hemostatics; D015842:Serine Proteinase Inhibitors; D007611:Aprotinin