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Intravenous vs. Intraosseous administration of drugs during cardiac arrest (NLS 616): Systematic Review

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CoSTR Citation:

de Almeida MF, Guinsburg R, Velaphi S, Aziz K, Perlman JM, Szyld E, Kim HS, Hosono S, Liley HG, Mildenhall L, Trevsianuto D, Kapadia VS, Rabi Y, Isayama I, Roehr CC, Schmoelzer G, Avis S, Anderson L, Wyllie JP and Wyckoff MH. Intravenous vs. intraosseus administration of drugs during cardiac arrest. [Internet] Brussels, Belgium. International Liaison Committee on Resuscitation (ILCOR) Neonatal Life Support Task Force, December 18, 2019. Available from http://ilcor.org

Collaborators

The Advanced Life Support and Pediatric Life Support Task Forces at the International Liaison Committee on Resuscitation (ILCOR).

Methodological Preamble and Link to Published Systematic Review

The continuous evidence process for the production of Consensus on Science with Treatment Recommendations (CoSTR) started with a systematic review of available literature regarding the Intravenous vs. intraosseous administration of drugs during cardiac arrest (Granfeldt A, 2019, PROSPERO ### https://www.xxx ). Evidence for neonatal literature was sought and considered by Life Support task forces. These data were taken into account when formulating the Treatment Recommendations.

Systematic Review

Granfeldt A, Avis SR, Lind PC, Holmberg MJ, Kleinman M, Maconochie I, Hsu CH, de Almeida MF, Wang T-L, Neumar RW, and Andersen LW for the International Liaison Committee on Resuscitation’s (ILCOR) Neonatal Life Support, Paediatric Life Support, and Advanced Life Support Task Forces. Intravenous vs. Intraosseous administration of drugs during cardiac arrest: a systematic review. Resuscitation (submitted 2020).

The PICOST

(Population, Intervention, Comparator, Outcome, Study Designs, and Time Frame)

  • Population: Neonates in any setting (in-hospital or out-of-hospital) with cardiac arrest (includes severe bradycardia and inadequate perfusion requiring chest compressions).
  • Intervention: Placement of an intraosseous (IO) cannula and drug administration through this IO during cardiac arrest.
  • Comparison: Placement of an intravenous (IV) cannula (umbilical vein in newly born infants) and drug administration through this IV during cardiac arrest.
  • Outcomes:
  • Death during event, within 24 hours and before hospital discharge;
  • § Long term neurodevelopmental outcomes;
  • ROSC: any signs of cardiac output with HR > 60bpm, and time to ROSC;
  • Brain Injury [HIE stage 2-3 Sarnat (term only), IVH Grades III-IV, PVL (preterm only);
  • § Time to secure access;
  • Morbidity related to IO (osteomylitis, fracture, epiphyseal plate injury, compartment syndrome) or to IV (extravasation, embolic phenomenon, phlebitis)

Study Designs:

  • Inclusion criteria: Randomized trials, non-randomized controlled trials, and observational studies (cohort studies and case-control studies) comparing IO to IV administration of drugs; Randomized trials assessing the effect of specific drugs (e.g. epinephrine) in subgroups related to IO vs. IV administration; Studies assessing cost-effectiveness for a descriptive summary.
  • Exclusion Criteria: Ecological studies, case series, case reports, reviews, abstracts, editorials, comments, letters to the editor, or unpublished studies
  • Search: All years and all languages were included as long as there was an English abstract. Medline (OVID interface), Embase (OVID interface), Cochrane Central Register of Controlled Trials – 1946 to Sep 12, 2019, and ongoing trials on International Clinical Trials Registry Plataform

A priori subgroups to be examined:

Cardiac and non-cardiac causes of circulatory collapse; Gestational Age [preterm <37 weeks and term >= 37 weeks]; Delivery Room OR other site; Hospital OR out of hospital; Central OR peripheral IV access; Paediatric trained personnel vs non paediatric.

PROSPERO Registration: XXX

Consensus on Science

For the critical outcome of death during event, within 24 hours or before hospital discharge, no evidence was identified regarding IO versus IV placement in neonates with severe bradycardia and inadequate perfusion requiring chest compressions in any setting (in-hospital or out-of-hospital).

For the critical outcome of long term neurodevelopmental outcomes, no evidence was identified regarding IO versus IV placement in neonates with severe bradycardia and inadequate perfusion requiring chest compressions in any setting (in-hospital or out-of-hospital).

For the critical outcome of return of spontaneous circulation (ROSC), no evidence was identified regarding IO versus IV placement in neonates with severe bradycardia and inadequate perfusion requiring chest compressions in any setting (in-hospital or out-of-hospital).

For the critical outcome of brain injury, no evidence was identified regarding IO versus IV placement in neonates with severe bradycardia and inadequate perfusion requiring chest compressions in any setting
(in-hospital or out-of-hospital).

For the critical outcome of time to secure access, no evidence was identified regarding IO versus IV placement in neonates with severe bradycardia and inadequate perfusion requiring chest compressions in any setting (in-hospital or out-of-hospital).

For the critical outcome of morbidity related to IO placement, no evidence was identified regarding IO versus IV placement in neonates with severe bradycardia and inadequate perfusion requiring chest compressions in any setting (in-hospital or out-of-hospital).

No evidence was identified on placement of an IO cannula and drug administration through this IO in neonates with severe bradycardia and inadequate perfusion requiring chest compressions in the delivery room.

Treatment Recommendations

We suggest 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 during newborn resuscitation is a reasonable alternative (weak recommendation, very low certainty of evidence).

Outside the delivery room setting, we suggest that either umbilical venous access or the intraosseous route may be used to administer fluids and medications during newborn resuscitation (weak recommendation, very low certainty of evidence). The actual route used may depend on local availability of equipment, training and experience.

Justification and Evidence to Decision Highlights

In making this recommendation we recognize the absence of data from human neonatal studies supporting any advantage of intraosseous over umbilical venous access. There are a number of case reports of serious adverse effects of intraosseous access in neonates, including tibial fractures, extravasation of fluid and medications resulting in compartment syndrome and amputation {Vidal 1993 1201; Katz 1994 258; Ellemunter 1999 F74; Carreras-Gonzales 2012 233; Oesterlie 2014 413; Suominen 2015 1389}.

The rate of adverse effects attributable to emergency umbilical venous catheterization is unknown. However, public feedback emphasized umbilical access as the technique most commonly taught and used whilst recognizing that intraosseous access may be helpful in out of hospital settingsor in neonatal or pediatric in intensive care neonatal units.

Knowledge Gaps

There are many gaps related to IO access and umbilical vein access in newborn during resuscitation due to the absence of clinical trials, cohort studies and case-control studies. Even case series or case reports are not available on IO administration in neonatal resuscitation in the delivery room or in emergency department or out of hospital deliveries.

Specific research is required in preterm and term neonates:

  • Determination time from start of CPR to achieve successful IO placement;
  • Determination time from start of CPR to achieve successful IV umbilical vein placement;
  • Optimal IO device suitable for newly born infants;
  • Position of IO device (head of humerus, proximal tibia, other) to successful IO access;
  • Short and long-term safety of IO placement during newborn resuscitation;
  • Complications related to emergency umbilical venous catheterization;
  • Pharmacokinetics and plasma availability of IO compared to IV administration of drugs;
  • Training for IO placement and IV umbilical vein placement during neonatal resuscitation;
  • How to best secure and maintain any emergency vascular access devices;
  • Optimal method to determine correct placement of any emergency vascular access device;
  • Do animal and simulation models translate to clinical practice?
  • IO access during neonatal resuscitation outside the delivery room.

Attachments

EtD Table: NLS-616-IO-vs-IV-Et D

References

Carreras-González E, Brió-Sanagustín S, Guimerá I, Crespo C. [Complication of the intraosseous route in a newborn infant]. Med Intensiva. 2012 Apr;36(3):233-4.

Ellemunter H, Simma B, Trawöger R, Maurer H. Intraosseous lines in preterm and full term neonates. Arch Dis Child Fetal Neonatal Ed. 1999 Jan;80(1):F74-5.

Katz DS, Wojtowycz AR. Tibial fracture: a complication of intraosseous infusion. Am J Emerg Med. 1994 Mar;12(2):258-9.

Oesterlie GE, Petersen KK, Knudsen L, Henriksen TB. Crural amputation of a newborn as a consequence of intraosseous needle insertion and calcium infusion. Pediatr Emerg Care. 2014 Jun;30(6):413-4.

Suominen PK, Nurmi E, Lauerma K. Intraosseous access in neonates and infants: risk of severe complications - a case report. Acta Anaesthesiol Scand. 2015 Nov;59(10):1389-93.

Vidal R, Kissoon N, Gayle M. Compartment syndrome following intraosseous infusion. Pediatrics. 1993 Jun;91(6):1201-2.


Task Force Systematic Review

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