Intravenous vs. intraosseous administration of drugs during cardiac arrest: A systematic review

doi:10.1016/j.resuscitation.2020.02.025

Resuscitation

Volume 149, April 2020, Pages 150-157

https://doi.org/10.1016/j.resuscitation.2020.02.025 Get rights and content

Abstract

Aim

To perform a systematic review of the literature on intravenous (IV) vs. intraosseous (IO) administration of drugs during cardiac arrest in order to inform an update of international guidelines.

Methods

The review was performed according to PRISMA guidelines and registered on PROSPERO. Medline, Embase and Evidence-Based Medicine Reviews were searched on December 17, 2019 for studies comparing IV to IO administration of drugs. The population included neonatal, paediatric, and adult patients with cardiac arrest. Two investigators reviewed each search for study relevance, extracted data, and assessed the risk of bias of individual studies. Meta-analyses were performed for studies without a critical risk of bias. Certainty of evidence was evaluated using GRADE.

Results

We included six observational studies comparing IV to IO administration of drugs and two randomized trials assessing the effect of specific drugs in subgroups related to IV vs. IO administration. All studies included adult out-of-hospital cardiac arrest patients. No studies were identified in neonatal or paediatric patients. The risk of bias for the observational studies was overall assessed as critical or serious, with confounding and selection bias being the primary sources of bias. The meta-analyses excluding studies with a critical risk of bias favoured IV access for all outcomes. Using GRADE, the certainty of evidence was judged at very low. Subgroup analyses of the two randomized trials demonstrated no statistically significant interactions between the route of access and study drugs on outcomes. However, these trials were underpowered to assess such interactions.

Conclusions

We identified a limited number of studies comparing IV vs. IO administration of drugs during cardiac arrest. Pooled results from four observational studies favoured IV access with very low certainty of evidence. From the subgroup analyses of two randomized clinical trials, there was no statistically significant interaction between the route of access and study drug on outcomes.

Introduction

Current guidelines recommend administration of certain drugs (e.g. epinephrine and amiodarone/lidocaine) as part of advanced life support during cardiac arrest.1, 2, 3, 4 Owing to the relative ease of intraosseous (IO) access, it has gained significant focus during the last decade as an option for drug administration during cardiac arrest in all age groups. In addition, many Emergency Medical Service agencies and in-hospital resuscitation teams use IO as the first choice of access for drug administration during cardiac arrest. Guidelines recommend that drugs can be administered through an IO route if intravenous (IV) access is difficult or impossible to obtain.1, 2 However, it is unknown whether the IO route is comparable to the IV route for drug effectiveness and patient outcomes. The aim of this study was to perform a systematic review of the literature on IV vs. IO administration of drugs during cardiac arrest in order to inform an update of international guidelines.

Section snippets

Protocol and registration

The protocol for the current study was prospectively submitted to the International Prospective Register of Systematic Reviews (PROSPERO) on Sept. 14, 2019 (registration number CRD42020150877). The protocol is provided in the Supplementary contents. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.⁵ The PRISMA checklist is provided in the Supplementary contents. The review was commissioned by the International Liaison

Study selection

Search 1 identified 309 unique titles/abstracts, of which 283 were excluded based on initial review of the abstracts (Kappa = 0.71, eFig. 1). After full-text review, an additional 21 studies were excluded for various reasons, leaving 5 studies for inclusion (Kappa = 0.92).12, 13, 14, 15, 16 We identified one additional observational study published after the last search.¹⁷

In search 2, 1114 unique titles/abstracts were identified, of which 1098 were excluded based on initial review of the

Discussion

In this systematic review on IV vs. IO administration of drugs during cardiac arrest, only a limited number of studies were identified. This included six adult observational studies and two subgroup analyses from randomized trials. Pooled estimates from the observational studies favoured IV access but with very low certainty of evidence. Subgroup analysis of the ALPS and PARAMEDIC2 trial demonstrated no statistically significant interaction between route of access and study drug on outcomes. No

Conclusion

We identified a limited number of studies comparing IV vs. IO administration of drugs during cardiac arrest. Pooled results from four adult observational studies favoured IV access with very low certainty of evidence. From the subgroup analyses of two randomized clinical trials, there was no statistically significant interaction between the route of access and study drug on outcomes. No studies were identified in neonates or children.

Conflicts of interest

None of the authors have any financial conflicts of interests and none of the authors have academic conflicts related to ongoing or planned trials. Lars W. Andersen was compensated by the American Heart Association on behalf of ILCOR for his work related to this systematic review.

Acknowledgements

The authors would like to thank Carolyn Ziegler, information specialist at the St Michael’s Hospital Health Sciences Library, Li Ka Shing Knowledge Institute Toronto, ON, Canada, for preparing and conducting the systematic searches.

International Liaison Committee on Resuscitation’s (ILCOR) Advanced Life Support task force: Lars W. Andersen, Katherine M. Berg, Bernd W. Böttiger, Clifton W. Callaway, Charles D. Deakin, Michael W. Donnino, Ian R. Drennan, Cindy H. Hsu, Peter Morley, Tonia C.

References (45)

C.D. Deakin et al.
European Resuscitation Council guidelines for resuscitation 2010 section 4. Adult advanced life support
Resuscitation
(2010)
F. Sanfilippo et al.
Amiodarone or lidocaine for cardiac arrest: a systematic review and meta-analysis
Resuscitation
(2016)
M.J. Holmberg et al.
Vasopressors during adult cardiac arrest: a systematic review and meta-analysis
Resuscitation
(2019)
B.A. Feinstein et al.
Intraosseous compared to intravenous drug resuscitation in out-of-hospital cardiac arrest
Resuscitation
(2017)
T. Kawano et al.
Intraosseous vascular access is associated with lower survival and neurologic recovery among patients with out-of-hospital cardiac arrest
Ann Emerg Med
(2018)
B. Clemency et al.
Intravenous vs. intraosseous access and return of spontaneous circulation during out of hospital cardiac arrest
Am J Emerg Med
(2017)
L. Nguyen et al.
Effect of intravenous versus intraosseous access in prehospital cardiac arrest
Air Med J
(2019)
P. Mody et al.
Intraosseous versus intravenous access in patients with out-of-hospital cardiac arrest: insights from the resuscitation outcomes consortium continuous chest compression trial
Resuscitation
(2019)
L.W. Andersen et al.
“Resuscitation time bias”—a unique challenge for observational cardiac arrest research
Resuscitation
(2018)
L.W. Andersen et al.
Epinephrine in cardiac arrest — insights from observational studies
Resuscitation
(2018)

S.L. Hoskins et al.

Pharmacokinetics of intraosseous and central venous drug delivery during cardiopulmonary resuscitation

Resuscitation

(2012)

B.A. Leidel et al.

Comparison of intraosseous versus central venous vascular access in adults under resuscitation in the emergency department with inaccessible peripheral veins

Resuscitation

(2012)

R. Reades et al.

Intraosseous versus intravenous vascular access during out-of-hospital cardiac arrest: a randomized controlled trial

Ann Emerg Med

(2011)

D. Wampler et al.

Paramedics successfully perform humeral EZ-IO intraosseous access in adult out-of-hospital cardiac arrest patients

Am J Emerg Med

(2012)

W.C. Dalsey et al.

Comparison of superior vena caval and inferior vena caval access using a radioisotope technique during normal perfusion and cardiopulmonary resuscitation

Ann Emerg Med

(1984)

J.M. Burgert et al.

Pharmacokinetic effects of endotracheal, intraosseous, and intravenous epinephrine in a swine model of traumatic cardiac arrest

Am J Emerg Med

(2019)

M.R. Wong et al.

Effects of intraosseous epinephrine in a cardiac arrest swine model

J Surg Res

(2016)

I.K. Maconochie et al.

European resuscitation council guidelines for resuscitation 2015: section 6. Paediatric life support

Resuscitation

(2015)

D. Maxien et al.

Intraosseous needles in pediatric cadavers: rate of malposition

Resuscitation

(2019)

J. Wyllie et al.

European Resuscitation Council guidelines for resuscitation 2015: section 7. Resuscitation and support of transition of babies at birth

Resuscitation

(2015)

J. Soar et al.

Part 4: advanced life support: 2015 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations

Resuscitation

(2015)

M.S. Link et al.

Part 7: adult advanced cardiovascular life support: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care

Circulation

(2015)

Cited by (51)

Route of drug administration in out-of-hospital cardiac arrest: A protocol for a randomised controlled trial (PARAMEDIC-3)
2024, Resuscitation Plus
The PARAMEDIC-3 trial evaluates the clinical and cost-effectiveness of an intraosseous first strategy, compared with an intravenous first strategy, for drug administration in adults who have sustained an out-of-hospital cardiac arrest.
PARAMEDIC-3 is a pragmatic, allocation concealed, open-label, multi-centre, superiority randomised controlled trial. It will recruit 15,000 patients across English and Welsh ambulance services. Adults who have sustained an out-of-hospital cardiac arrest are individually randomised to an intraosseous access first strategy or intravenous access first strategy in a 1:1 ratio through an opaque, sealed envelope system. The randomised allocation determines the route used for the first two attempts at vascular access. Participants are initially enrolled under a deferred consent model.
The primary clinical-effectiveness outcome is survival at 30-days. Secondary outcomes include return of spontaneous circulation, neurological functional outcome, and health-related quality of life. Participants are followed-up to six-months following cardiac arrest. The primary health economic outcome is incremental cost per quality-adjusted life year gained.
The PARAMEDIC-3 trial will provide key information on the clinical and cost-effectiveness of drug route in out-of-hospital cardiac arrest.
Trial registration: ISRCTN14223494, registered 16/08/2021, prospectively registered.
The association of tibial vs. humeral intraosseous vascular access with patient outcomes in adult out-of-hospital cardiac arrests
2023, Resuscitation
Humeral and tibial intraosseous (IO) vascular access can deliver resuscitative medications for out-of-hospital cardiac arrest (OHCA), however the optimal site is unclear. We examined the association between IO tibia vs. humerus as the first-attempted vascular access site with OHCA outcomes.
We used prospectively-collected data from the British Columbia Cardiac Arrest registry, including adult OHCAs treated with IO humerus or IO tibia as the first-attempted intra-arrest vascular access. We fit logistic regression models on the full study cohort and a propensity-matched cohort, to estimate the association between IO site and both favorable neurological outcomes (Cerebral Performance Category 1–2) and survival at hospital discharge.
We included 1041 (43%) and 1404 (57%) OHCAs for whom IO humerus and tibia, respectively, were the first-attempted intra-arrest vascular access. Among humerus and tibia cases, 1010 (97%) and 1369 (98%) had first-attempt success, and the median paramedic arrival-to-successful access interval was 6.7 minutes (IQR 4.4–9.4) and 6.1 minutes (IQR 4.1–8.9), respectively. In the propensity-matched cohort (n = 2052), 31 (3.0%) and 44 (4.3%) cases had favourable neurological outcomes in the IO humerus and IO tibia groups, respectively; compared to IO humerus, we did not detect an association between IO tibia with favorable neurological outcomes (OR 1.44; 95% CI 0.90–2.29) or survival to hospital discharge (OR 1.29; 95% CI 0.83–2.01). Results using the full cohort were similar.
We did not detect an association between the first-attempted intra-arrest IO site (tibia vs. humerus) and clinical outcomes. Clinical trials are warranted to test differences between vascular access strategies.
Trends in use of intraosseous and intravenous access in out-of-hospital cardiac arrest across English ambulance services: A registry-based, cohort study
2023, Resuscitation
The optimum route for drug administration in cardiac arrest is unclear. Recent data suggest that use of the intraosseous route may be increasing. This study aimed to explore changes over time in use of the intraosseous and intravenous drug routes in out-of-hospital cardiac arrest in England.
We extracted data from the UK Out-of-Hospital Cardiac Arrest Outcomes registry. We included adult out-of-hospital cardiac arrest patients between 2015–2020 who were treated by an English Emergency Medical Service that submitted vascular access route data to the registry. The primary outcome was any use of the intraosseous route during cardiac arrest. We used logistic regression models to describe the association between time (calendar month) and intraosseous use.
We identified 75,343 adults in cardiac arrest treated by seven Emergency Medical Service systems between January 2015 and December 2020. The median age was 72 years, 64% were male and 23% presented in a shockable rhythm. Over the study period, the percentage of patients receiving intraosseous access increased from 22.8% in 2015 to 42.5% in 2020. For each study-month, the odds of receiving any intraosseous access increased by 1.019 (95% confidence interval 1.019 to 1.020, p < 0.001). This observed effect was consistent across sensitivity analyses. We observed a corresponding decrease in use of intravenous access.
In England, the use of intraosseous access in out-of-hospital cardiac arrest has progressively increased over time. There is an urgent need for randomised controlled trials to evaluate the clinical effectiveness of the different vascular access routes in cardiac arrest.
Intravenous vs. intraosseous vascular access during out-of-hospital cardiac arrest – protocol for a randomised clinical trial
2023, Resuscitation Plus
During cardiac arrest, current guidelines recommend attempting intravenous access first and to consider intraosseous access if intravenous access is unsuccessful or impossible. However, these recommendations are only based on very low-certainty evidence. Therefore, the “Intravenous vs Intraosseous Vascular Access During Out-of-Hospital Cardiac Arrest“ (IVIO) trial aims to determine whether there is a difference in patient outcomes depending on the type of vascular access attempted during out-of-hospital cardiac arrest. This current article describes the clinical IVIO trial.
The IVIO trial is an investigator-initiated, randomised trial of intravenous vs. intraosseous vascular access during adult non-traumatic out-of-hospital cardiac arrest in Denmark. The intervention will consist of minimum two attempts (if unsuccessful on the first attempt) to successfully establish intravenous or intraosseous vascular access during cardiac arrest. The intraosseous group will be further randomised to the humeral or tibial site. The primary outcome is sustained return of spontaneous circulation and key secondary outcomes include survival and survival with a favourable neurological outcome at 30 days. A total of 1,470 patients will be included.
The trial started in March 2022 and the last patient is anticipated to be included in the spring of 2024. The primary results will be reported after 90-day follow-up and are anticipated in mid-2024.
The current article describes the design of the Danish IVIO trial. The findings of this trial will help inform future guidelines for selecting the optimal vascular access route during out-of-hospital cardiac arrest.
Focused Ultrasonography in Cardiac Arrest
2023, Emergency Medicine Clinics of North America
Out-of-Hospital Cardiac Arrest
2023, Emergency Medicine Clinics of North America

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: The members of the International Liaison Committee on Resuscitation’s (ILCOR) Neonatal Life Support, Paediatric Life Support, and Advanced Life Support Task Forces are listed at the end of the article.

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ReviewIntravenous vs. intraosseous administration of drugs during cardiac arrest: A systematic review

Abstract

Aim

Methods

Results

Conclusions

Introduction

Section snippets

Protocol and registration

Study selection

Discussion

Conclusion

Conflicts of interest

Acknowledgements

Resuscitation

Resuscitation

Resuscitation

Resuscitation

Ann Emerg Med

Am J Emerg Med

Air Med J

Resuscitation

Resuscitation

Resuscitation

Resuscitation

Resuscitation

Ann Emerg Med

Am J Emerg Med

Ann Emerg Med

Am J Emerg Med

J Surg Res

Resuscitation

Resuscitation

Resuscitation

Part 4: advanced life support: 2015 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations

Resuscitation

Part 7: adult advanced cardiovascular life support: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care

Circulation

Review
Intravenous vs. intraosseous administration of drugs during cardiac arrest: A systematic review