@article {Sankaranfetalneonatal-2020-321034, author = {Deepika Sankaran and Praveen K Chandrasekharan and Sylvia F Gugino and Carmon Koenigsknecht and Justin Helman and Jayasree Nair and Bobby Mathew and Munmun Rawat and Payam Vali and Lori Nielsen and Daniel J Tancredi and Satyan Lakshminrusimha}, title = {Randomised trial of epinephrine dose and flush volume in term newborn lambs}, elocation-id = {fetalneonatal-2020-321034}, year = {2021}, doi = {10.1136/archdischild-2020-321034}, publisher = {BMJ Publishing Group}, abstract = {Objectives Neonatal resuscitation guidelines recommend 0.5{\textendash}1 mL saline flush following 0.01{\textendash}0.03 mg/kg of epinephrine via low umbilical venous catheter for persistent bradycardia despite effective positive pressure ventilation (PPV) and chest compressions (CC). We evaluated the effects of 1 mL vs 3 mL/kg flush volumes and 0.01 vs 0.03 mg/kg doses on return of spontaneous circulation (ROSC) and epinephrine pharmacokinetics in lambs with cardiac arrest.Design Forty term lambs in cardiac arrest were randomised to receive 0.01 or 0.03 mg/kg epinephrine followed by 1 mL or 3 mL/kg flush after effective PPV and CC. Epinephrine (with 1 mL flush) was repeated every 3 min until ROSC or until 20 min. Haemodynamics, blood gases and plasma epinephrine concentrations were monitored.Results Ten lambs had ROSC before epinephrine administration and 2 died during instrumentation. Among 28 lambs that received epinephrine, 2/6 in 0.01 mg/kg-1 mL flush, 3/6 in 0.01 mg/kg-3 mL/kg flush, 5/7 in 0.03 mg/kg-1 mL flush and 9/9 in 0.03 mg/kg-3 mL/kg flush achieved ROSC (p=0.02). ROSC was five times faster with 0.03 mg/kg epinephrine compared with 0.01 mg/kg (adjusted HR (95\% CI) 5.08 (1.7 to 15.25)) and three times faster with 3 mL/kg flush compared with 1 mL flush (3.5 (1.27 to 9.71)). Plasma epinephrine concentrations were higher with 0.01 mg/kg-3 mL/kg flush (adjusted geometric mean ratio 6.0 (1.4 to 25.7)), 0.03 mg/kg-1 mL flush (11.3 (2.1 to 60.3)) and 0.03 mg/kg-3 mL/kg flush (11.0 (2.2 to 55.3)) compared with 0.01 mg/kg-1 mL flush.Conclusions 0.03 mg/kg epinephrine dose with 3 mL/kg flush volume is associated with the highest ROSC rate, increases peak plasma epinephrine concentrations and hastens time to ROSC. Clinical trials evaluating optimal epinephrine dose and flush volume are warranted.}, issn = {1359-2998}, URL = {https://fn.bmj.com/content/early/2021/03/08/archdischild-2020-321034}, eprint = {https://fn.bmj.com/content/early/2021/03/08/archdischild-2020-321034.full.pdf}, journal = {Archives of Disease in Childhood - Fetal and Neonatal Edition} }