Bioavailability of endotracheal epinephrine in an ovine model of neonatal resuscitation

Jayasree Nair, Payam Vali, Sylvia F. Gugino, Carmon Koenigsknecht, Justin Helman, Lori C. Nielsen, Praveen Chandrasekharan, Munmun Rawat, Sara Berkelhamer, Bobby Mathew, Satyanarayana Lakshminrusimha

Research output: Contribution to journalArticle

Abstract

Background: Distressed infants in the delivery room and those that have completed postnatal transition are both resuscitated according to established neonatal resuscitation guidelines, often with endotracheal (ET) epinephrine at the same dose. We hypothesized that ET epinephrine would have higher bioavailability in a post-transitional compared to transitioning newborn model due to absence of fetal lung liquid and intra-cardiac shunts. Methods: 15 term fetal (transitioning newborn) and 6 postnatal lambs were asphyxiated by umbilical cord and ET tube occlusion respectively. Lambs were resuscitated after 5 min of asystole. ET epinephrine (0.1 mg/kg) was administered after 1 min of positive pressure ventilation (PPV) and chest compressions, and repeated 3 min later, followed by intravenous (IV) epinephrine (0.03 mg/kg) every 3 min until return of spontaneous circulation (ROSC). Serial plasma epinephrine concentrations were measured. Results: Peak plasma epinephrine concentrations were lower in transitioning newborns as compared to postnatal lambs: after a single ET dose (145.36 ± 135.5 ng/ml vs 553.54 ± 215 ng/ml, p < 0.01) and after two ET doses (443 ± 192.49 ng/ml vs 1406 ± 420.8 ng/ml, p < 0.01). The rates of ROSC with a single ET dose were similar in both groups (40% vs 50% in newborn and postnatal respectively, p > 0.99). There was a higher incidence of post-ROSC tachycardia and increased carotid blood flow in the postnatal group. Conclusions: In the postnatal period, ET epinephrine at currently recommended doses resulted in higher peak epinephrine concentrations, post-ROSC tachycardia and cerebral reperfusion without significant differences in incidence of ROSC. Further studies evaluating the optimal dose of ET epinephrine during the postnatal period are warranted.

LanguageEnglish (US)
Pages27-32
Number of pages6
JournalEarly Human Development
Volume130
DOIs
StatePublished - Mar 1 2019

Fingerprint

Resuscitation
Biological Availability
Epinephrine
Sheep
Newborn Infant
Tachycardia
Cerebrovascular Circulation
Delivery Rooms
Positive-Pressure Respiration
Umbilical Cord
Incidence
Heart Arrest
Reperfusion
Thorax
Guidelines
Lung

Keywords

  • Endotracheal epinephrine
  • Epinephrine concentration
  • Lung liquid
  • Neonatal resuscitation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology

Cite this

Bioavailability of endotracheal epinephrine in an ovine model of neonatal resuscitation. / Nair, Jayasree; Vali, Payam; Gugino, Sylvia F.; Koenigsknecht, Carmon; Helman, Justin; Nielsen, Lori C.; Chandrasekharan, Praveen; Rawat, Munmun; Berkelhamer, Sara; Mathew, Bobby; Lakshminrusimha, Satyanarayana.

In: Early Human Development, Vol. 130, 01.03.2019, p. 27-32.

Research output: Contribution to journalArticle

Nair, J, Vali, P, Gugino, SF, Koenigsknecht, C, Helman, J, Nielsen, LC, Chandrasekharan, P, Rawat, M, Berkelhamer, S, Mathew, B & Lakshminrusimha, S 2019, 'Bioavailability of endotracheal epinephrine in an ovine model of neonatal resuscitation', Early Human Development, vol. 130, pp. 27-32. https://doi.org/10.1016/j.earlhumdev.2019.01.006
Nair, Jayasree ; Vali, Payam ; Gugino, Sylvia F. ; Koenigsknecht, Carmon ; Helman, Justin ; Nielsen, Lori C. ; Chandrasekharan, Praveen ; Rawat, Munmun ; Berkelhamer, Sara ; Mathew, Bobby ; Lakshminrusimha, Satyanarayana. / Bioavailability of endotracheal epinephrine in an ovine model of neonatal resuscitation. In: Early Human Development. 2019 ; Vol. 130. pp. 27-32.
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abstract = "Background: Distressed infants in the delivery room and those that have completed postnatal transition are both resuscitated according to established neonatal resuscitation guidelines, often with endotracheal (ET) epinephrine at the same dose. We hypothesized that ET epinephrine would have higher bioavailability in a post-transitional compared to transitioning newborn model due to absence of fetal lung liquid and intra-cardiac shunts. Methods: 15 term fetal (transitioning newborn) and 6 postnatal lambs were asphyxiated by umbilical cord and ET tube occlusion respectively. Lambs were resuscitated after 5 min of asystole. ET epinephrine (0.1 mg/kg) was administered after 1 min of positive pressure ventilation (PPV) and chest compressions, and repeated 3 min later, followed by intravenous (IV) epinephrine (0.03 mg/kg) every 3 min until return of spontaneous circulation (ROSC). Serial plasma epinephrine concentrations were measured. Results: Peak plasma epinephrine concentrations were lower in transitioning newborns as compared to postnatal lambs: after a single ET dose (145.36 ± 135.5 ng/ml vs 553.54 ± 215 ng/ml, p < 0.01) and after two ET doses (443 ± 192.49 ng/ml vs 1406 ± 420.8 ng/ml, p < 0.01). The rates of ROSC with a single ET dose were similar in both groups (40{\%} vs 50{\%} in newborn and postnatal respectively, p > 0.99). There was a higher incidence of post-ROSC tachycardia and increased carotid blood flow in the postnatal group. Conclusions: In the postnatal period, ET epinephrine at currently recommended doses resulted in higher peak epinephrine concentrations, post-ROSC tachycardia and cerebral reperfusion without significant differences in incidence of ROSC. Further studies evaluating the optimal dose of ET epinephrine during the postnatal period are warranted.",
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T1 - Bioavailability of endotracheal epinephrine in an ovine model of neonatal resuscitation

AU - Nair, Jayasree

AU - Vali, Payam

AU - Gugino, Sylvia F.

AU - Koenigsknecht, Carmon

AU - Helman, Justin

AU - Nielsen, Lori C.

AU - Chandrasekharan, Praveen

AU - Rawat, Munmun

AU - Berkelhamer, Sara

AU - Mathew, Bobby

AU - Lakshminrusimha, Satyanarayana

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Background: Distressed infants in the delivery room and those that have completed postnatal transition are both resuscitated according to established neonatal resuscitation guidelines, often with endotracheal (ET) epinephrine at the same dose. We hypothesized that ET epinephrine would have higher bioavailability in a post-transitional compared to transitioning newborn model due to absence of fetal lung liquid and intra-cardiac shunts. Methods: 15 term fetal (transitioning newborn) and 6 postnatal lambs were asphyxiated by umbilical cord and ET tube occlusion respectively. Lambs were resuscitated after 5 min of asystole. ET epinephrine (0.1 mg/kg) was administered after 1 min of positive pressure ventilation (PPV) and chest compressions, and repeated 3 min later, followed by intravenous (IV) epinephrine (0.03 mg/kg) every 3 min until return of spontaneous circulation (ROSC). Serial plasma epinephrine concentrations were measured. Results: Peak plasma epinephrine concentrations were lower in transitioning newborns as compared to postnatal lambs: after a single ET dose (145.36 ± 135.5 ng/ml vs 553.54 ± 215 ng/ml, p < 0.01) and after two ET doses (443 ± 192.49 ng/ml vs 1406 ± 420.8 ng/ml, p < 0.01). The rates of ROSC with a single ET dose were similar in both groups (40% vs 50% in newborn and postnatal respectively, p > 0.99). There was a higher incidence of post-ROSC tachycardia and increased carotid blood flow in the postnatal group. Conclusions: In the postnatal period, ET epinephrine at currently recommended doses resulted in higher peak epinephrine concentrations, post-ROSC tachycardia and cerebral reperfusion without significant differences in incidence of ROSC. Further studies evaluating the optimal dose of ET epinephrine during the postnatal period are warranted.

AB - Background: Distressed infants in the delivery room and those that have completed postnatal transition are both resuscitated according to established neonatal resuscitation guidelines, often with endotracheal (ET) epinephrine at the same dose. We hypothesized that ET epinephrine would have higher bioavailability in a post-transitional compared to transitioning newborn model due to absence of fetal lung liquid and intra-cardiac shunts. Methods: 15 term fetal (transitioning newborn) and 6 postnatal lambs were asphyxiated by umbilical cord and ET tube occlusion respectively. Lambs were resuscitated after 5 min of asystole. ET epinephrine (0.1 mg/kg) was administered after 1 min of positive pressure ventilation (PPV) and chest compressions, and repeated 3 min later, followed by intravenous (IV) epinephrine (0.03 mg/kg) every 3 min until return of spontaneous circulation (ROSC). Serial plasma epinephrine concentrations were measured. Results: Peak plasma epinephrine concentrations were lower in transitioning newborns as compared to postnatal lambs: after a single ET dose (145.36 ± 135.5 ng/ml vs 553.54 ± 215 ng/ml, p < 0.01) and after two ET doses (443 ± 192.49 ng/ml vs 1406 ± 420.8 ng/ml, p < 0.01). The rates of ROSC with a single ET dose were similar in both groups (40% vs 50% in newborn and postnatal respectively, p > 0.99). There was a higher incidence of post-ROSC tachycardia and increased carotid blood flow in the postnatal group. Conclusions: In the postnatal period, ET epinephrine at currently recommended doses resulted in higher peak epinephrine concentrations, post-ROSC tachycardia and cerebral reperfusion without significant differences in incidence of ROSC. Further studies evaluating the optimal dose of ET epinephrine during the postnatal period are warranted.

KW - Endotracheal epinephrine

KW - Epinephrine concentration

KW - Lung liquid

KW - Neonatal resuscitation

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