PT  - JOURNAL ARTICLE
AU  - Deepika Sankaran
AU  - Praveen K Chandrasekharan
AU  - Sylvia F Gugino
AU  - Carmon Koenigsknecht
AU  - Justin Helman
AU  - Jayasree Nair
AU  - Bobby Mathew
AU  - Munmun Rawat
AU  - Payam Vali
AU  - Lori Nielsen
AU  - Daniel J Tancredi
AU  - Satyan Lakshminrusimha
TI  - Randomised trial of epinephrine dose and flush volume in term newborn lambs
AID  - 10.1136/archdischild-2020-321034
DP  - 2021 Mar 09
TA  - Archives of Disease in Childhood - Fetal and Neonatal Edition
PG  - fetalneonatal-2020-321034
4099  - http://fn.bmj.com/content/early/2021/03/08/archdischild-2020-321034.short
4100  - http://fn.bmj.com/content/early/2021/03/08/archdischild-2020-321034.full
AB  - Objectives Neonatal resuscitation guidelines recommend 0.5–1 mL saline flush following 0.01–0.03 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.