title: Prolonged Activated Clotting Time after Protamine Administration Does Not Indicate Residual Heparinization after Cardiopulmonary Bypass in Pediatric Open Heart Surgery.
abstract: BACKGROUND
  In open heart surgery, heparinization is commonly neutralized using an empirical heparin:protamine ratio ranging between 1:1 and 1:1.5. However, these ratios may result in protamine overdose that should be avoided for its negative side effects on the coagulation system. This study aimed to indicate the appropriate treatment for prolonged activated clotting time (ACT) after protamine administration following cardiopulmonary bypass (CPB) in pediatric open heart surgery by investigating the underlying reasons for it.
  
  
  METHODS
  Twenty-seven children (<10 kg) undergoing open heart surgery were included. Heparin was administered only before CPB (400 IU/kg) and in the pump priming volume for CPB (2,000 IU) and was neutralized by 1:1 protamine after CPB. The blood heparin concentration was measured using anti-Xa assay. ACT and blood concentrations of heparin, coagulation factors, thrombin-antithrombin complex, and prothrombin fragment 1 + 2 were assessed. A rotational thromboelastometry (ROTEM; Tem International GmbH, München, Bayern, Germany) was used to confirm the coagulation status and residual heparin after protamine administration.
  
  
  RESULTS
  Anti-Xa assay showed that there is no residual heparin in the blood after 1:1 protamine administration. Nevertheless, ACT (128.89 ± 3.09 seconds before heparin administration) remained prolonged (177.14 ± 5.43 seconds at 10 minutes after protamine, 182.00 ± 5.90 seconds at 30 minutes after protamine). The blood concentrations of coagulation factors were significantly lower than those before heparin administration (p < 0.01). The low FIBTEM MCF of ROTEM (4.43 ± 0.32 mm) at 10 minutes after protamine indicated low fibrinogen concentration.
  
  
  CONCLUSIONS
  Prolonged ACT after heparin neutralization by 1:1 protamine administration does not necessarily indicate residual heparin, but low blood concentrations of coagulation factors should be considered as a reason as well. Accordingly, supply of coagulation factors instead of additional protamine should be considered.
authors.affiliation: Department of Pediatric Anesthesiology and Critical Care Medicine, Asklepios Clinic Sankt Augustin, German Pediatric Heart Center, Sankt Augustin, Germany.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Pediatric Anesthesiology and Critical Care Medicine, Asklepios Clinic Sankt Augustin, German Pediatric Heart Center, Sankt Augustin, Germany.
authors.forename: Hans-Gerd
authors.initials: HG
authors.lastname: Wolf
authors.affiliation: Department of Pediatric Cardiac Surgery, Asklepios Clinic Sankt Augustin, German Pediatric Heart Center, Sankt Augustin, Germany.
authors.forename: Nicodème
authors.initials: N
authors.lastname: Sinzobahamvya
authors.affiliation: Department of Pediatric Cardiac Surgery, Asklepios Clinic Sankt Augustin, German Pediatric Heart Center, Sankt Augustin, Germany.
authors.forename: Boulos
authors.initials: B
authors.lastname: Asfour
authors.affiliation: Department of Pediatric Cardiac Surgery, Asklepios Clinic Sankt Augustin, German Pediatric Heart Center, Sankt Augustin, Germany.
authors.forename: Victor
authors.initials: V
authors.lastname: Hraska
authors.affiliation: Department of Pediatric Anesthesiology and Critical Care Medicine, Asklepios Clinic Sankt Augustin, German Pediatric Heart Center, Sankt Augustin, Germany.
authors.forename: Ehrenfried
authors.initials: E
authors.lastname: Schindler
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects; D002315:Cardiopulmonary Bypass / Q000009:adverse effects / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005858:Germany; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000601:surgery*; D006493:Heparin / Q000008:administration & dosage / Q000097:blood*; D006494:Heparin Antagonists / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D008297:Male; D011182:Postoperative Care / Q000379:methods; D011300:Preoperative Care / Q000379:methods; D011479:Protamines / Q000008:administration & dosage*; D018570:Risk Assessment; D013916:Thrombelastography / Q000379:methods; D016896:Treatment Outcome; D014914:Whole Blood Coagulation Time
chemical_list: D000925:Anticoagulants; D006494:Heparin Antagonists; D011479:Protamines; D006493:Heparin