The effectiveness of low dose tranexamic acid in primary cardiac surgery

Wayne Lambert FRCPC Frances J. Brisebois B VHAXMMR P~RMS ~f Tim J. Wharton RN :[: Renald C. Carrier V NCVC CCV :I: David Boyle ~V.CPC Brian H. Rowe MSC CCFV w IJurpose: This randomized controlled clinical trial compared three doses oftranexamic acid el-A) in primary cardiac surgery in terms of blood loss and transfusion requirements. M e t h o d s : Patients presenting for primary coronary artery bypass grafting (CABG) and/or valve replacement were randomly assigned to one of three TA regimens : 20 mg'kg-I (LD), 50 mg'kg -I (MD), and 100 mg-kg"l (HD). All participants and staff were blinded to the allocation. Haemoglobin (Hgb), haematocrit and platelet count were determined preoperatively, after bypass, at CCA arrival, and 12 and 24 hr after surgery. Coagulation parameters were measured before and after surgery. Blood loss was measured intraoperatively and for 24 hr postoperatively following a standardized protocol. Blood products were administered in a standardized fashion. Results: Two hundred twenty patients completed the trial over 10 months: 74 in LD, 75 in MD and 72 in HD dose groups. All patient groups were comparable; similar procedures were performed in each group. No differences were identified for blood loss intra-operatively (490  232 ml, 523  413 ml, 488  357 ml, respectively), 24 hr post-operatively (543 _ 223 ml, 544 _+ 23 I, 458 _ 210 ml, respectively), and overall (I 032  358 ml, 1067 _+ 502 ml, 946 _ 459 ml, respectively). Blood product administration was similar in the three groups. No differences in postoperative complications were found. Conclusions: This study demonstrates the equivalency of the three doses of TA in primary cardiac surgical procedures. The use'of low dose (20 mg-kg-q) TA results in comparable outcomes, without additional complications. O b j e c t i f : Cet essai clinique contr616 randomis~ a compar~ trois doses d'acide tranexamique (AT), Iors d'une cardiochirurgie primaire, en termes de pertes sanguines et de besoins transfusionnels. M & h o d e s : Des patients qui se pr&entent pour un pontage aorto-coronaire primaire et / ou pour un remplacement valvulaire ont regu de fa~on al~atoire I'un des trois r~gimes d'AT : 20 mg.kg"l (dose faible DF), 50 mg'kgj (dose moyenne DM) et 100 mg-kg"j (dose ~lev& DE). La r~partition dans les groupes s'est faite ~ I'insu des participants et du personnel. Les taux d'h6moglobine (Hb) et d'h~matocrites ainsi que le d&ompte des plaquettes ont ~t~ faits avant I'op&ation, apr& le pontage, ~ rarriv& ~ I'unit~ des soins intensifs coronariens et, 12h et 24h apr~s la chirurgie. Les param&res de coagulation ont ~t~ mesur& avant et apr& la chirurgie. Les pertes sanguines ont ~t(~ mesur~es pendant I'op~ration et pendant les 24 heures qui ont suivi I'intervention, selon un protocole standardis& Les produits sanguins ont ~t~ administr& de far classique. R~sultats : l'essai a exig~ 10 mois et la participation de deux cent vingt patients : 74 dans le groupe ~ DF, 75 DM et 72 ~ DE. Tousles groupes de patients &aient semblables ; des traitements similaires ont ~t~ r~alis& darts chaque groupe. Aucune diff&ence de perte sanguine n'a &6 identifi& pendant rop&ation (490 ml _ 232 ml, 523 ml - 413 ml, 488 ml _ 357 ml respectivement) et au total (I 032 ml __+358 ml, 1067 ml  502 ml, 946 ml  459 ml respectivement). I'administration de produit sanguin &ait similaire darts les trois groupes. Aucune diff&ence n'a &~ constat~e dans les complications postop&atoires. C o n c l u s i o n : Cette &ude d~montre des effets 6quivalents de trois doses d'AT dans la conduite de la cardiochirurgie primaire. I'utilisation d'une dose faible (20 mg.kg-~) d'AT amine des r&ultats comparables ~ rutilisation d'une dose moyenne ou 61ev& sans complications suppl~mentaires. - MPAIRED haemostasis and excessive postoperI cardiopulmonary bypass. 1 One method to ative bleeding are common complications o f reduce bleeding in the post-operative period is the use oftranexamic acid (TA). 2 In this study we evaluated whether reducing the dose o f TA used in our institution would modify blood loss and transfusion requirements in patients undergoing primary cardiac surgery requiring cardiopulmonary bypass. Methods After Ethics Review Board approval, informed consent was obtained from 225 patients 18 yr scheduled for primary coronary artery bypass grafting (CABG) a n d / o r valve replacement during 1996. Patients were randomized to one o f three groups using the MosesOakford m e t h o d ) Patients were excluded if they were: actively bleeding, receiving iv heparin, emergency cases, in renal failure, had received Warfarin within seven days, had a personal/family history o f bleeding, were Jehovah's witnesses or were having redo surgery. Four were excluded later due to inappropriate inclusion (2 H D , 1 LD) and late refusal (1HD). After anaesthesia induction, all patients received TA (20 mg.kg-1, 50 mg.kg-1, or 100 mg-kg-1) as a single bolus infusion over 30 min using coded infusion bags which were identical in appearance, transparency, and volume. Standard transfusion and perfusion protocols were employed. Haemoglobin (Hgb), haematocrit and platelet count were determined before surgery, after bypass, at CCA arrival, and 12 and 24 hr after surgery. Prothrombin time (PT), activated partial prothrombin time (aPTT), fibrinogen and D-dimers were determined before and after surgery. Demographic data (age, sex), medical history, and outcome (length of stay, blood loss, transfusion requirements, complications) information were collected. The primary outcome was total blood loss. Secondary outcomes included red blood cell transfusion requirements, per mortality, re-thoracotomy and postoperative CNS complications. Intra-operative and post-operative blood losses were measured in a standardized fashion. Sample size was determined using data from a pilot study. Data were analysed using the SPSS-PC statistical software program (Version 4.0.1: SPSS, Inc.; Chicago, IL). Categorical values are reported as counts (%), and compared using 2 statistics. Continuous variables are reported as means and analysed using analysis o f variance (ANOVA). P < 0.01 was used as the threshold for statistical significance. Intraclass correlation coefficient TABLE I Post-operative blood work and main outcomes HBG 106.8  HCT .31  Placelet 135.9  Post-op 12 hr HBG 109  HCT 0.32  Platelet 146.5  Post-op 24 hr HBG 106  HCT 0.31  Platelet 142.0 +43.2 *P < .05;tP < .01; loss of blood results do not include two patients who died. Mean  SD L a m b e r t et al.: TRANEXAMIC ACID TABLE II Blood product administration Results Two hundred twenty one patients completed the study. All patient groups were comparable; similar procedures were performed in each group. All patient groups had similar laboratory values in the post-operative period (Table I). No differences were found among the groups with respect to blood loss in any period except the 12-24 hr while in the CCA. Comp (...truncated)