Age-Dependent Heterogeneity in the Efficacy of Prophylaxis With Enoxaparin Against Catheter-Associated Thrombosis in Critically Ill Children: A Post Hoc Analysis of a Bayesian Phase 2b Randomized Clinical Trial. Issue 4 (21st January 2021)

• Record Type: Journal Article
• Authors: Faustino, E. Vincent S.; Raffini, Leslie J.; Hanson, Sheila J.; Cholette, Jill M.; Pinto, Matthew G.; Li, Simon; Kandil, Sarah B.; Nellis, Marianne E.; Shabanova, Veronika; Silva, Cicero T.; Tala, Joana A.; McPartland, Tara; Spinella, Philip C.
• Other Names: other.; contributor.; Faustino E. Vincent S. author non-byline.; Spinella Philip author non-byline.; Raffini Leslie author non-byline.; Kandil Sarah author non-byline.; McPartland Tara author non-byline.; Awan Asaad author non-byline.; Hummel Amy author non-byline.; Duplin Matthew author non-byline.; contributor.; Odesina Oluwanisola author non-byline.; contributor.; Shabanova Veronika author non-byline.; Stolar Marilyn author non-byline.; Hu Xin author non-byline.; contributor.; Lin I-Hsin author non-byline.; contributor.; Silva Cicero T. author non-byline.; Epelman Monica author non-byline.; contributor.; Navarro Oscar M. author non-byline.; contributor.; Chima Ranjit author non-byline.; Branchford Brian author non-byline.; Weiss Theresa author non-byline.; contributor.; Zelterman Daniel author non-byline.; contributor.; Sharathkumar Anjali author non-byline.; contributor.; Polikoff Lee author non-byline.; contributor.; Hanson Sheila author non-byline.; Nelson Tom author non-byline.; Plunk Matthew author non-byline.; Shad Sadaf author non-byline.; contributor.; Siegel Katherine author non-byline.; contributor.; Higgerson Renee author non-byline.; Christie LeeAnn author non-byline.; Guleria Saurabh author non-byline.; Padilla-Tolentino Eimeira author non-byline.; contributor.; Ragsdale Carolyn E. author non-byline.; contributor.; Li Simon author non-byline.; Pinto Matthew author non-byline.; Brudnicki Adele R. author non-byline.; Cuddy William author non-byline.; contributor.; Michalowska-Suterska Malgorzata author non-byline.; contributor.; Spinella Philip C. author non-byline.; Abrahm Manju author non-byline.; Barrale Tina author non-byline.; Camazine Maraya author non-byline.; DaFonseca Juliana author non-byline.; Huff Meghan author non-byline.; Mehanovic-Varmaz Lana author non-byline.; Nicholas Jennifer author non-byline.; Rider Brad author non-byline.; Rogers Sharon author non-byline.; Schafer Stephanie author non-byline.; contributor.; Thomas Kimberly A. author non-byline.; contributor.; Cholette Jill M. author non-byline.; Bean Stephen A. author non-byline.; Chess Mitchell author non-byline.; Cole Carole author non-byline.; contributor.; Taillie Eileen author non-byline.; contributor.; Nellis Marianne E. author non-byline.; Kovanlikaya Arzu author non-byline.; Rivera-Lopez Antonio author non-byline.; contributor.; Small Keshia O. author non-byline.; contributor.; Faustino E. Vincent S. author non-byline.; Gupta Anjali author non-byline.; Hayes Nancy author non-byline.; Kandil Sarah author non-byline.; Rhieu Joana author non-byline.; Silva Cicero T. author non-byline.; contributor.; Tala Joana author non-byline.;
• Is Part Of: Critical care medicine. Volume 49:Issue 4(2021)
• Page Start: e369
• Page End: e380
• Publication Date: 2021-01-21
• Subjects: central venous catheter -- deep venous thrombosis -- infant -- platelet -- thrombin; Critical care medicine -- Periodicals; Soins intensifs -- Périodiques; 616.028
• DOI: 10.1097/CCM.0000000000004848
• Languages: English
• ISSNs: 0090-3493

Abstract

Abstract : Supplemental Digital Content is available in the text. Abstract : OBJECTIVES: We explored the age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin against central venous catheter-associated deep venous thrombosis in critically ill children. DESIGN: Post hoc analysis of a Bayesian phase 2b randomized clinical trial. SETTING: Seven PICUs. PATIENTS: Children less than 18 years old with newly inserted central venous catheter. INTERVENTIONS: Enoxaparin started less than 24 hours after insertion of central venous catheter and adjusted to anti-Xa level of 0.2–0.5 international units/mL versus usual care. MEASUREMENTS AND MAIN RESULTS: Of 51 children randomized, 24 were infants less than 1 year old. Risk ratios of central venous catheter-associated deep venous thrombosis with prophylaxis with enoxaparin were 0.98 (95% credible interval, 0.37–2.44) in infants and 0.24 (95% credible interval, 0.04–0.82) in older children greater than or equal to 1 year old. Infants and older children achieved anti-Xa level greater than or equal to 0.2 international units/mL at comparable times. While central venous catheter was in situ, endogenous thrombin potential, a measure of thrombin generation, was 223.21 nM.min (95% CI, 8.78–437.64 nM.min) lower in infants. Factor VIII activity, a driver of thrombin generation, was also lower in infants by 45.1% (95% CI, 15.7–74.4%). Median minimum platelet count while central venous catheter was in situ was higher in infants by 39 × 10 3 /mm 3 (interquartile range, 17–61 × 10 3 /mm 3 ). Central venous catheter:vein ratio was not statistically different. Prophylaxis with enoxaparin was less efficacious against central venous catheter-associated deep venous thrombosis at lower factor VIII activity and at higher platelet count. CONCLUSIONS: The relatively lesser contribution of thrombin generation on central venous catheter-associated thrombus formation in critically ill infants potentially explains the age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin.