1. Randomised trial of epinephrine dose and flush volume in term newborn lambs
- Author
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Munmun Rawat, Daniel J. Tancredi, Justin Helman, Sylvia F. Gugino, Praveen Chandrasekharan, Carmon Koenigsknecht, Lori Nielsen, Payam Vali, Jayasree Nair, Deepika Sankaran, Satyan Lakshminrusimha, and Bobby Mathew
- Subjects
Resuscitation ,Umbilical Veins ,resuscitation ,Hemodynamics ,Heart Massage ,Saline flush ,Cardiovascular ,Pediatrics ,Peripheral ,Positive-Pressure Respiration ,0302 clinical medicine ,Medicine ,030212 general & internal medicine ,Original Research ,Obstetrics and Gynecology ,General Medicine ,Adrenergic beta-Agonists ,Epinephrine ,Treatment Outcome ,Anesthesia ,cardiology ,medicine.symptom ,Drug ,Drug Monitoring ,medicine.drug ,Bradycardia ,Clinical Trials and Supportive Activities ,Return of spontaneous circulation ,neonatology ,Catheterization ,Dose-Response Relationship ,Paediatrics and Reproductive Medicine ,03 medical and health sciences ,Pharmacokinetics ,Clinical Research ,030225 pediatrics ,Coronary Circulation ,Catheterization, Peripheral ,Animals ,Sheep ,Dose-Response Relationship, Drug ,business.industry ,Newborn ,Cardiopulmonary Resuscitation ,Heart Arrest ,Brain Disorders ,Volume (thermodynamics) ,Animals, Newborn ,Pediatrics, Perinatology and Child Health ,business - Abstract
ObjectivesNeonatal 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.DesignForty 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.ResultsTen 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.Conclusions0.03 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.
- Published
- 2021