Drug Therapy and Vascular Access

Intraosseous Versus Umbilical Vein Routes of Fluid and Drug Administration During Newborn Resuscitation

Last Full Review: ILCOR 2020

What is the best route of access for fluids and drugs during newborn resuscitation from cardiac arrest?

 

Evidence Summary

A 2020 International Liaison Committee on Resuscitation (ILCOR) systematic review (Granfeldt, Avis, and Lind 2020, 150) and Consensus on Science with Treatment Recommendations  (Wyckoff et al. 2020, S185) evaluated the evidence for placement of an intraosseous (IO) cannula and drug administration through this intraosseous (IO) during neonatal cardiac arrest (including severe bradycardia/inadequate perfusion requiring chest compressions) compared with placement of an intravenous (IV) cannula or umbilical vein cannula in newborns) and drug administration through this cannula during cardiac arrest. Outcomes included death during the event, within 24 hours and before hospital discharge; long-term neurodevelopmental outcomes; return of spontaneous circulation (ROSC) with a heart rate greater than 60 beats per minute and time to ROSC; brain injury; time to secure access; and morbidity related to the IO or IV cannula.

For all outcomes, no evidence was identified on the placement of an IO cannula compared with IV placement and drug administration in neonates with severe bradycardia and inadequate perfusion requiring chest compressions in any setting (Granfeldt, Avis, and Lind 2020, 150). Six case reports (very low-certainty evidence) were noted that described serious adverse effects of IO access in neonates, such as tibial fractures or extravasation of fluid and medications resulting in compartment syndrome and amputation (Vidal, Kissoon, and Gayle 1993, 1201; Katz and Wojtowycz 1994, 258; Ellemunter et al. 1999, F74; Carreras-González et al. 2012, 233; Oesterlie et al. 2014, 413; Suominen, Nurmi, and Lauerma 2015, 1389). No reports of adverse effects or complications from umbilical vein catheterization were remarked on (Granfeldt, Avis, and Lind 2020, 150).

A weak recommendation by ILCOR suggests use of umbilical venous catheterization as the primary method of vascular access during newborn resuscitation in the delivery room. If umbilical venous access is not feasible, the intraosseous route as vascular access is a reasonable alternative during newborn resuscitation (Wyckoff et al. 2020, S185).

Outside of the delivery room setting, it is suggested that either umbilical venous access or the intraosseous route may be used to administer fluids and medications during newborn resuscitation, and the route use may depend on local availability of equipment, training and experience (Wyckoff et al. 2020, S185).

Insights and Implications

The recommendation is made in the absence of data from studies of neonates supporting any advantage of intraosseous over umbilical venous access and in light of case reports of complications in neonates from the IO approach. Umbilical access is the technique most commonly taught for neonates although it is acknowledged in the consensus review that in the out-of-hospital setting or in pediatric or neonatal intensive care units, an intraosseous approach may be helpful.

Dose, Route, and Interval of Epinephrine for Neonatal Resuscitation

Last Full Review: ILCOR 2019

What are the evidence-based recommendations for epinephrine dosing, dose interval, and route of delivery for neonates of any gestation less than 28 days of age and who have no detected cardiac output, asystole or a heart rate less than 60 beats/minute despite ventilation and chest compression?

 

Evidence Summary

A 2019 International Liaison Committee on Resuscitation (ILCOR) systematic review and Consensus on Science with Treatment Recommendations (CoSTR) (Wyckoff et al. 2020, S185) evaluated any non-standard dose, interval or route of epinephrine compared with use of epinephrine doses of 0.01 to 0.03 milligrams per kilogram (mg/kg) intravenously at intervals of every 3 to 5 minutes in neonates of any gestation less than 28 days of age who have no detected cardiac output or who have asystole or heart rate less than 60 beats per minute despite ventilation and chest compressions.

Two observational studies were identified, both in term and preterm infants, that addressed the comparisons (Halling et al. 2017, 232;(Barber and Wyckoff 2006, 1028). Both studies were from a single neonatal unit, with participants from different time periods.

Very low-certainty evidence (downgraded for very serious risk of bias and very serious imprecision) from one observational study in 50 neonates treated with epinephrine reported no significant difference between the initial administration of epinephrine by endotracheal tube (0.03 mg/kg/dose) compared with initial intravenous administration (0.01 mg/kg/dose) for the outcome of death before hospital discharge (Halling et al. 2017, 232). This same study showed no difference in the time to return of spontaneous circulation (ROSC) for endotracheal versus intravenous epinephrine.

Very low-certainty evidence (downgraded for very serious risk of bias and very serious imprecision) from two observational studies (Halling et al. 2017, 232; Barber and Wyckoff 2006, 1028) with 97 neonates treated with epinephrine showed no significant difference between the initial endotracheal administration of epinephrine compared with initial IV administration for the outcome of failure to achieve ROSC (RR, 0.97; 95% CI, 0.38–2.48; P=0.96; aRD, 7 fewer; 95% CI, 135 fewer to 322 more per 1,000 neonates did not achieve ROSC) (Wyckoff et al. 2020, S185).

No other eligible studies were identified for comparing different routes of administration, different doses or intervals of epinephrine administration, or other pre-specified outcomes.

If the heart rate has not increased to more than 60 beats per minute after optimizing ventilation and chest compressions, ILCOR suggests the administration of intravascular epinephrine, 0.01 to 0.03 mg/kg (Wyckoff et al. 2020, S185).

If intravascular access is not yet available, ILCOR suggests administering endotracheal epinephrine at a larger dose (0.05 to 0.1 mg/kg) (Wyckoff et al. 2020, S185). A weak recommendation is made that administration of endotracheal epinephrine should not delay attempts to establish vascular access (Wyckoff et al. 2020, S185).

A weak recommendation by ILCOR suggests the administration of further doses of epinephrine every 3 to 5 minutes, preferably intravascularly, if the heart rate remains less than 60 beats per minute (Wyckoff et al. 2020, S185).

If the response to endotracheal epinephrine is inadequate, ILCOR suggests that an intravascular dose be given as soon as vascular access is obtained, regardless of the interval (Wyckoff et al. 2020, S185).

Insights and Implications

The recommendations are based on very low-certainty evidence from two cohort studies that showed similar survival and ROSC following administration of epinephrine by endotracheal versus intravenous routes. The ILCOR CoSTR reviewers note, however, one neonatal animal study of asphyxia arrest that reported higher and faster epinephrine concentrations, shorter time to ROSC, and higher rates of ROSC after central venous epinephrine administration compared with endotracheal epinephrine (Wyckoff et al. 2020, S185).