IV vs. IO administration of drugs during cardiac arrest (adult) (ALS): Systematic Review

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This Review is a draft version prepared by ILCOR, with the purpose to allow the public to comment and is labeled “Draft for Public Comment". The comments will be considered by ILCOR. The next version will be labelled “draft" to comply with copyright rules of journals. The final Review will be published on this website once a summary article has been published in a scientific Journal and labeled as “final”.

Conflict of Interest Declaration

The ILCOR Continuous Evidence Evaluation process is guided by a rigorous ILCOR Conflict of Interest policy.

The following Task Force members and other authors declared an intellectual conflict of interest and this was acknowledged and managed by the Task Force Chairs and Conflict of Interest committees: Jerry Nolan, Charles Deakin

CoSTR Citation

Granfeldt A, Avis SR, Lind PC, Holmberg MJ, Kleinman M, Maconochie I, Hsu CH, de Almeida F, Wang TL, Neumar RW, and Andersen LW for the International Liaison Committee on Resuscitation’s (ILCOR) Advanced Life Support Task Force. Intravenous vs. intraosseous administration of drugs during cardiac arrest: A systematic review. Consensus on Science with Treatment Recommendations [Internet]. Brussels, Belgium: International Liaison Committee on Resuscitation (ILCOR) Advanced Life Support Task Force. 3 January 2020 Available from: http://ilcor.org

Methodological Preamble and Link to Published Systematic Review

The continuous evidence evaluation process for the production of the Consensus on Science with Treatment Recommendations (CoSTR) started with a systematic review that was approved by the ILCOR Scientific Advisory Committee and involved clinical content experts (registered with PROSPERO on September 9, 2019). Evidence from adult literature was sought and considered by the Advanced Life Support Adult Task Force.

Systematic Review

Granfeldt A, Avis SR, Lind PC, Holmberg MJ, Kleinman M, Maconochie I, Hsu CH, de Almeida F, Wang TL, 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. In preparation.

PICOST

The PICOST (Population, Intervention, Comparator, Outcome, Study Designs and Timeframe)

Population: Adults in any setting (in-hospital or out-of-hospital) with cardiac arrest.

Intervention: Placement of an intraosseous (IO) cannula and drug administration through this IO during cardiac arrest.

Comparators: Placement of an intravenous (IV) cannula and drug administration through this IV during cardiac arrest.

Outcomes: Return of spontaneous circulation, survival to hospital discharge, and survival to hospital discharge with a favorable neurological outcome.

Study Designs: Randomized trials, non-randomized controlled trials, and observational studies (cohort studies and case-control studies) comparing IO to IV administration of drugs will be included. Randomized trials assessing the effect of specific drugs (e.g. epinephrine and amiodarone/lidocaine) in subgroups related to IO vs. IV administration will also be included. Ecological studies, case series, case reports, reviews, abstracts, editorials, comments, letters to the editor, or unpublished studies will not be included.

Timeframe: All years and all languages were included as long as there was an English abstract; unpublished studies (e.g., conference abstracts, trial protocols) were excluded. Literature search updated to September 12, 2019.

Prospero Registration: CRD42020150877

Consensus on Science

For the important outcome of return of spontaneous circulation, we have identified very low certainty evidence (downgraded for risk of bias and inconsistency) from 3 observational studies (Feinstein 2017 91; Kawano 2017 588; Mody 2019 69) including 34,686 adult out-of-hospital cardiac arrests, which showed worse outcomes with the use of IO access when compared to IV access (adjusted OR: 0.74 [95%CI: 0.67 to 0.81], P < 0.00001; absolute risk difference: -6.1% [95%CI: -7.9 to -4.3] or 61 fewer per 1,000 cardiac arrest had return of spontaneous circulation with IO access compared to IV access [95%CI: 79 fewer to 43 fewer]).

For the critical outcome of survival to hospital discharge, we have identified very low certainty evidence (downgraded for risk of bias and inconsistency) from 3 observational studies (Feinstein 2017 91; Kawano 2017 588; Mody 2019 69) including 34,686 adult out-of-hospital cardiac arrests, which showed worse outcomes with the use of IO access when compared to IV access (adjusted OR: 0.79 [95%CI: 0.66 to 0.93], P = 0.005; absolute risk difference: -1.7% [95%CI: -2.7 to – 0.5] or 17 fewer per 1,000 cardiac arrest survival to hospital discharge with IO access compared to IV access [95%CI: 27 fewer to 5 fewer]).

For the critical outcome survival to hospital discharge with a favorable neurological outcome, we have identified very low certainty evidence (downgraded for risk of bias and inconsistency) from 2 observational studies (Kawano 2017 588; Mody 2019 69) including 32,886 adult out-of-hospital cardiac arrests. The overall quality of evidence was rated as very low primarily due to a very serious risk of bias and inconsistency. Because of this no meta-analysis was performed.

Treatment Recommendations

We suggest IV access as compared to IO access as the first attempt for drug administration during adult cardiac arrest (weak recommendation, very low-certainty evidence).

If attempts at IV access are unsuccessful or IV access is not feasible, we suggest IO access as a route for drug administration during adult cardiac arrest (weak recommendation, very low-certainty evidence).

Justification and Evidence to Decision Framework Highlights

Although the overall certainty in the evidence is very low, the current evidence suggests that outcomes might be better when drugs are administered intravenously as compared to intraosseously.

Current guidelines suggest that IO access should only be used if IV access is "difficult or impossible" (Soar 2015 110) or "not readily available" (Link 2015 S459). There is no new evidence to support a change to these guidelines.

Knowledge Gaps

  • There are no randomized clinical trials that directly compare IO vs. IV drug administration during cardiac arrest.
  • There are no randomized clinical trials that directly compare the different sites of IO access (e.g. tibial, humeral) during cardiac arrest.
  • It is unclear whether the effectiveness of an IO access is dependent on the drug administered (e.g. epinephrine vs. amiodarone/lidocaine), the dose, or the volume of injection and flush.

Attachments

Evidence-to-Decision Table: IV-vs.IO

References

References listed alphabetically by first author last name in this citation format

Feinstein BA, Stubbs BA, Rea T and Kudenchuk PJ. Intraosseous compared to intravenous drug resuscitation in out-of-hospital cardiac arrest. Resuscitation. 2017;117:91-96.

Kawano T, Grunau B, Scheuermeyer FX, Gibo K, Fordyce CB, Lin S, Stenstrom R, Schlamp R, Jenneson S and Christenson J. Intraosseous Vascular Access Is Associated With Lower Survival and Neurologic Recovery Among Patients With Out-of-Hospital Cardiac Arrest. Ann Emerg Med. 2018;71:588-596.

Link MS, Berkow LC, Kudenchuk PJ, Halperin HR, Hess EP, Moitra VK, Neumar RW, O'Neil BJ, Paxton JH, Silvers SM, White RD, Yannopoulos D and Donnino MW. Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015;132:S444-64.

Mody P, Brown SP, Kudenchuk PJ, Chan PS, Khera R, Ayers C, Pandey A, Kern KB, de Lemos JA, Link MS and Idris AH. Intraosseous versus intravenous access in patients with out-of-hospital cardiac arrest: Insights from the resuscitation outcomes consortium continuous chest compression trial. Resuscitation. 2019;134:69-75.

Soar J, Nolan JP, Bottiger BW, Perkins GD, Lott C, Carli P, Pellis T, Sandroni C, Skrifvars MB, Smith GB, Sunde K, Deakin CD and Adult advanced life support section C. European Resuscitation Council Guidelines for Resuscitation 2015: Section 3. Adult advanced life support. Resuscitation. 2015;95:100-47.


Task Force Systematic Review

Discussion

GUEST
Michael Rushing (266 posts)
When comparing humeral IO to IV placement I have found that medication is just as fast by humeral IO.
Reply
GUEST
Cindy Hsu (266 posts)
Thank you for your comment. We did not identify any human studies that directly compared the rate of drug infusion between humeral IO vs IV during cardiac arrest. As such, there is insufficient evidence for making any conclusions on this topic.

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