Abstract

BACKGROUND Surgical craniosynostosis repair in children is associated with massive blood loss and significant transfusion of blood products. Fibrinogen concentrate is claimed to be useful in reducing blood loss and transfusion requirements. OBJECTIVE We investigated whether prophylactic administration of fibrinogen concentrate will reduce blood loss and transfusion requirements during paediatric craniofacial surgery. DESIGN Randomised, placebo-controlled, double-blind clinical trial. SETTING University medical centre. PATIENTS A total of 114 infants and children up to 25 months of age (median age 10 months). INTERVENTION Surgical craniosynostosis repair by calvarial remodelling was performed in each patient. Patients were randomised to receive prophylactic fibrinogen concentrate (Haemocomplettan P) at a mean dose of 79 mg kg body weight or placebo. MAIN OUTCOME MEASURES Primary outcome was the volume of transfused blood products. Secondary outcomes were peri-operative blood loss, duration of surgery, length of stay in the paediatric ICU, length of hospital stay, postoperative complications and adverse effects of fibrinogen concentrate infusion. RESULTS No significant differences (P < 0.05) were found in the volume of transfused blood products (median 29 ml kg body weight vs. 29 ml kg body weight), intra-operative estimated blood loss (45 vs. 46 ml kg), calculated blood loss (57 vs. 53 ml kg), or postoperative blood loss (24 vs. 24 ml kg) between the intervention and placebo groups. In addition, duration of surgery, length of stay in the paediatric ICU, hospital stay and complications were not significantly different between the two groups. CONCLUSION During surgical craniosynostosis repair in young children, prophylactic administration of high-dose fibrinogen concentrate did not reduce the amount of transfused blood products or decrease peri-operative blood loss. TRIAL REGISTRATION National Trial Register (NTR2975) and EudraCT (2011-002287-24).

Abstract

The Platelets for Neonatal Thrombocytopenia (PlaNeT-2) trial reported an unexpected overall benefit of a prophylactic platelet transfusion threshold of 25x109/L compared to 50x109/L for major bleeding and/or mortality in preterm neonates (7% absolute risk reduction). However, some neonates in the trial may have experienced little benefit or even harm from the 25x109/L threshold. We aimed to assess this heterogeneity of treatment effect in the PlaNet-2 trial, in order to investigate whether all preterm neonates benefit from the low threshold. We developed a multivariable logistic regression model in the PlaNet-2 data to predict baseline risk of major bleeding and/or mortality for all 653 neonates. We then ranked the neonates based on their predicted baseline risk and categorized them into four risk quartiles. Within these quartiles we assessed absolute risk difference between the 50x109/L and 25x109/L threshold group. A total of 146 neonates died or developed major bleeding. The internally validated C-statistic of the model was 0.63 (95% confidence interval 0.58 - 0.68). The 25x109/L threshold was associated with absolute risk reduction in all risk groups, varying from 4.9% in the lowest to 12.3% in the highest risk group. These results suggest that a 25x109/L prophylactic platelet count threshold can be adopted in all preterm neonates, irrespective of predicted baseline outcome risk. Future studies are needed to improve the predictive accuracy of the baseline risk model. Current Controlled Trials number ISRCTN87736839.