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 Nov 01
TA  - Archives of Disease in Childhood - Fetal and Neonatal Edition
PG  - 578--583
VI  - 106
IP  - 6
4099  - http://fn.bmj.com/content/106/6/578.short
4100  - http://fn.bmj.com/content/106/6/578.full
SO  - Arch Dis Child Fetal Neonatal Ed2021 Nov 01; 106
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.Data are available on reasonable request.