Oxygen titration during pediatric cardiac arrest (PLS #396): Scoping 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 were recused from the discussion as they declared a conflict of interest: None applicable

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: None applicable

Task Force Scoping Review Citation

Ong G, Maconochie I, Aicken R, Atkins DL, Bingham R, Couto TB, de Caen A, Guerguerian AM, Nadkarni V, Ng KC, Nuthall G, Reis A , Schexynader S, Tijssen J Van de Voorde P, Rabi J. on behalf of the International Liaison Committee on Resuscitation Paediatric Life Support Task Force. Oxygen titration during pediatric cardiac arrest. Scoping Review. Pediatric Life Support Task Force Insights [Internet] Brussels, Belgium: International Liaison Committee on Resuscitation (ILCOR) Education, Implementation, and Teams Task Force, 2020 January 03. Available from: http://ilcor.org

Methodological Preamble

The continuous evidence evaluation process started with a scoping review of basic life support conducted by the ILCOR PLS Task Force Scoping Review team. Evidence for pediatric literature was sought and considered by the Pediatric Task Force group.

Scoping Review

Pending

PICOST

PICOST

Description (with recommended text)

Population

Among infants and children who are in cardiac arrest in any setting (P)?

Intervention

does an FiO2 titrated to oxygenation during cardiac arrest (I),

Comparison

compared with the use of 100% oxygen (C),

Outcomes

Any clinical outcome.

Study Design

Randomized controlled trials (RCTs) and non-randomized studies (non-randomized controlled trials, interrupted time series, controlled before-and-after studies, cohort studies) are eligible for inclusion.

If it is anticipated that there will be insufficient studies from which to draw a conclusion, case series may be included in the initial search.

Timeframe

New Scoping or Systematic Review search strategy: All years and all languages are included as long as there is an English abstract

Re-running existing search strategy: Since date of last search, or is not known, since 1st Jan 2009 (for 2010 PICO), and 1st January 2014 (for 2015 PICO).

Search Strategies

Articles for review are obtained by searching PubMed, EMBASE, Cochrane, and Allied Health Literature (CINAHL), for all entries from database inception to October 2019 (last searched on October 31, 2019).

Articles are using key terms “Oxygen”, “Pediatrics”, “Children”, “Infants”, “Oxygen”, “Cardiac arrest”, “Resuscitation”, and “Chest compression”; including their MESH terms, and Embase exploded terms. The actual search strategies used are listed in Appendix A at the end of this document.

Inclusion and Exclusion criteria

Inclusion criteria:

Meet the requirements of the PICOST above. If no human studies identified, animal studies will be included.

Exclusion criteria:

1. Case series/reports with <5 patients

2. Populations who were not in cardiac arrest (pre- and post- arrest).

3. Studies on titration of oxygen pre-arrest (critically ill) or post-ROSC

4. Newborn at delivery

5. Studies evaluating pre-arrest epidemiological variables and other intra-cardiac arrest interventions other than a) provision of oxygen at other concentrations and at 100% or b) titration with blood oxygen measurements

5. Continuous oxygen insufflation, sustained insufflation only studies were not included if 100% oxygen was uniformly provided.

6. Any non-paediatric studies

Data tables

As there were no human studies identified in the search, animal studies were reviewed and tabled for indirect evidence.

Study

Population

Intervention(s)

Control

Outcomes

Setting

Type

Comments

Immature (Pediatric) Animal Models

{Walson KH 2011 335-43}

Postnatal day 16-18 rats (n = 15; 5 per group).

2 Interventions:

1- 100% oxygen

2- 100% oxygen + IV polynitroxyl albumin (anti-oxidant)

Room air

- No differences in survival rates

- BP 1-hour post arrest: Room air vs 100% oxygen- 35 +/- 4 vs. 45 +/- 5 mm Hg; p<0.05

PaO2 (ABG) 1-hour post arrest: Room air vs 100% oxygen - 59 +/- 3 vs. 465 +/- 46 mm Hg; p<0.05

- pH (ABG) 1-hour post arrest: Room air vs 100% oxygen- 7.36 +/- 0.05 vs. 7.42 +/-0.03, p<0.05

- Oxidative stress: brain immunohistochemistry

- evidence of increased oxidative stress in group resuscitated with 100% compared the other 2 groups

- group resuscitated with 100% oxygen + anti-oxidant had similar results with group resuscitated with room air

Experimental, pediatric model

- Rats underwent asphyxial cardiac arrest for 9 min.

Rats were randomized to receive 100%

oxygen, room air, or 100% oxygen with polynitroxyl albumin intravenously, 0 and 30 min after resuscitation) for 1 hr from the start of cardiopulmonary resuscitation.

Shams recovered in 100% oxygen or room air after surgery.

RCT, non-blinded

Conclusions: Resuscitation with 100% oxygen leads to increased oxidative stress but this can be prevented by using 1) room air or 2) giving an antioxidant after ROSC with 100% oxygen resuscitation.

Remarks:

The provision of 100% oxygen extended beyond ROSC for 1 hour as per protocol.

{Marquez AM 2018 138:A278}

(conference abstract, pending publication review)

4-week-old female piglets with 7 minutes of asphyxia (n=25)

- 100% oxygen (n=10)

- 21% oxygen (n=10)

- Sham (n=5)

- 100% oxygen

- Room air (21% oxygen)

No difference between groups in survival (8/10 vs 8/10, p=1.0).

No difference between groups in

- systemic, coronary, or pulmonary hemodynamics

- cerebral blood flow at baseline, during asphyxia, during CPR, or post-ROSC.

- PbtO2 was higher with 100% than 21% during CPR (point estimate +54.9±26.7, p=0.04) and during the first 10 minutes post-ROSC (point estimate +505±41.4, p<0.001). No differences in maximal oxidative phosphorylation in either cerebral cortex or hippocampus between groups. In cortex, mtROS was higher with 100% compared to 21% during maximal oxidative phosphorylation (0.283 [0.275,0.290] vs 0.224 [0.205,0.239] H2O2 pmol/(s*ml), p<0.03).

Experimental, pediatric model

- Subjects underwent asphyxial cardiac arrest for 9 min and randomized to 100% vs 21% during CPR and 10 minutes post-ROSC. Subsequently all animals were given 21% oxygen.

RCT, blinded

Conclusions: Provision of 100% FiO2, compared to room air (21% FiO2) during CPR confers no difference in survival and is associated with cerebral hyperoxia and increased mtROS generation

Neonatal Animal Models

{Garcia-Hidalgo C 2018 400}

Systematic review of human and animal neonatal studies

- the studies included post-delivery animal studies 12H to 72H of life

100% oxygen

Any other concentration

- No human newborn studies identified

- 8 animal studies (n = 323 animals) comparing various oxygen concentrations during chest compression were identified.

- Pooled analysis showed no difference in mortality rates for animals resuscitated with air vs. 100% oxygen (risk ratio 1.04 [0.35, 3.08], I2 = 0%, p = 0.94).

- ROSC was also similar between groups with a mean difference of -3.8 [-29.7-22] s, I2 = 0%, p = 0.77.

- No difference in oxygen damage or adverse events were identified between groups.

-

Systematic review and meta-analysis of neonatalanimal studies

Conclusion: Air had similar time to ROSC and mortality as 100% oxygen during neonatal chest compression. A large randomized controlled clinical trial comparing air vs. 100% oxygen during neonatal chest compression is warranted

Remarks:

- heterogeneity of studies noted (including chest compression strategies, timing of provision of positive pressure ventilation and ventilation strategies; not just oxygen concentrations)

Mature Animal Models

{Vereczki V 2006 821-35}

Mature beagles

(n= 12, 6 per group)

- 100% oxygen

- 21% oxygen

- No differences in survival

- Systemic arterial pressure for the hyperoxic groups was significantly greater than that of the normoxic animals (141±9 versus 105±2 mm Hg; P < 0.01)

- pO2 for hyperoxic animals was significantly greater than that of the normoxic animals at 30 mins (384±68 s.e. versus 76±2 mm Hg; P = 0.001)

- Increased oxidative stress in hyperoxic group

- Stereological quantification of neuronal death at 24 h reperfusion showed a 40% reduction using normoxic compared with hyperoxic resuscitation.

Experimental, mature animal model

RCT, non-blinded

Conclusions: Post-ischemic hyperoxic ventilation promotes oxidative stress that exacerbates prelethal loss of pyruvate dehydrogenase and delayed hippocampal neuronal cell death. Need for clinical trials comparing the effects of different ventilatory oxygen levels on neurologic outcome after cardiac arrest.

Remarks:

- 100% oxygen was also given post ROSC (1 hour).

{Zwemer CF 1994 159-70}

Mature dogs (n=27)

- 100% oxygen (n=9)

- pretreatment with anti-oxidant + 100% oxygen (n=8)

- 21% oxygen (n=10)

- No differences in survival between groups

- Hyperoxically resuscitated dogs sustained significantly worse neurological deficit at 12 and 24 h (mean scores: 39 +/- 3 and 49 +/- 8, respectively) than did antioxidant pretreated resuscitated dogs (mean scores: 22 +/- 1, P = 0.0007 and 22 +/- 1, P = 0.004, respectively) and normoxically resuscitated dogs (mean scores: 28 +/- 4, P = 0.025 and 33 +/- 8, P = 0.041 respectively).

Experimental, mature animal model

RCT, non-blinded

Conclusion: Oxidative injury may have a major role in central nervous system dysfunction following successful resuscitation from 9 min of cardiac arrest.

Resuscitation from cardiac arrest with hyperoxic FIO2's may contribute to and further exacerbate neurologic dysfunction.

Task Force Insights

1. Why this topic was reviewed.

This topic was reviewed because it had not been reviewed by ILCOR since 2005.

Current Treatment Recommendations:

There is insufficient information to recommend for or against the use of any specific inspired oxygen concentration during and immediately after resuscitation from cardiac arrest. Until additional evidence is published, we support healthcare providers’ use of 100% oxygen during resuscitation (when available). Once circulation is restored, providers should monitor oxygen saturation and reduce the inspired oxygen concentration while ensuring adequate oxygen delivery.

2. Narrative summary of evidence identified

The task force identified no human studies that addressed this question. This scoping review has not identified sufficient evidence to prompt either a new systematic review or reconsideration of current resuscitation guidelines/treatment recommendations.

Animal studies

  • Included in the review were the following experimental studies:
  • There were two immature (pediatric) animal models {Walson 2011 335; Marquez 2018 138 } which were included in the review.
  • There was a systematic review and meta-analysis of neonatal animal studies {Garcia-Hidalgo 2018 400} and three neonatal animal studies reviewed {Dannevig 2013 163; Linner 2009 391; Solevåg 2016 7}. The three post-delivery neonatal animal studies were reviewed in the meta-analysis. Peri-delivery animal studies were excluded.
  • Two mature animal studies {Vereczki 2006 821; Zwemer 1994 159} were also reviewed.
  • Please refer to the table of animal studies for further details.
  • The experimental studies suggested no change between groups in the return of spontaneous circulation (ROSC) rates but provision of 100% oxygen during cardiac arrest resulted in more biochemical evidence of myocardial/cerebral oxidative stress. Only one mature animal study {Zwemer 1994 159} showed poorer short-term neurological dysfunction for survivors when 100% oxygen (compared to 21%) was provided during cardiac arrest.

3. Narrative Reporting of the task force discussions

As there were no human studies identified in the search to support a more specific systematic review, animal studies were reviewed for indirect evidence.

The reviewed animal studies showed no differences in survival rates. While there were biochemical and histological evidence of oxidative injuries, how these might influence long term neurological outcomes of these animals and clinical outcomes in the human pediatric population are unknown.

The following studies were considered in the evaluation of this topic. But were not included in the evidence table as they did not directly address the PICOST.

Pediatric population

An observational study {Cashen 2018 245} on pediatric extra-corporeal membrane oxygenation (ECMO) with a subgroup of patients (n=69/484) who received extracorporeal cardiopulmonary resuscitation (ECPR). This study assessed the incidence of hyperoxia and hypocapnia and their associated clinical outcomes. However, there was no data on oxygen titration during ECPR or prior to its initiation. Subgroup analysis and clinical associations with oxygen measurements were not performed due to the small numbers in the cardiac arrest subgroup.

The authors found that hyperoxia was common (68.4%) during pediatric extracorporeal membrane oxygenation in critically ill pediatric patients. Hyperoxia was associated with mortality (167 [50.5%] vs 48 [31.4%]; p < 0.001), but there was no difference in functional status among survivors.

Another observational study {Sutton 2019 1627} assessed the effect of ventilatory rates and pediatric in-hospital cardiac arrest survival outcomes. However, there was no data presented on oxygen titration or oxygen measurements during cardiac arrest. The study correlated ventilatory rates and survival to discharge and intra-cardiac arrest hemodynamics.

Adult population

One retrospective, observational study on adult OHCA (n=145) on the incidence of hyperoxemia {Spindelboeck 2013 770}. Intra-arrest, all were given 100% oxygen but hyperoxemia (14%) was associated with a higher rate of hospital admission but no differences in in-hospital CPC. There was no titration of oxygen during the cardiopulmonary resuscitation.

All newborns are currently recommended to receive 100% oxygen once chest compressions are initiated. Oxygen titration is done only during the initial resuscitation of the depressed newborn and after return of spontaneous circulation (or sustained heart rate > 60/min).

Due to poor circulation during chest compressions, pulse oximeters may not be able to reliably assess oxygenation. Oxygen titration during CPR may limited in the setting of patients with pre-existing intra-arterial monitoring in ICUs or during ECPR.

Knowledge Gaps

As there are no human studies that address intra-arrest oxygenation titration and provocative findings in animals, we feel there is sufficient equipoise to support an RCT addressing this question.

Potential populations for future investigation may include infants and children in the ICU setting with invasive blood monitoring or pediatric patients undergoing ECPR (albeit the mechanics are distinctly different from conventional CPR) to allow oxygen measurements and titration during cardiac arrest.

References

Cashen K, Reeder R, Dalton HJ, et al. Hyperoxia and Hypocapnia During Pediatric Extracorporeal Membrane Oxygenation: Associations With Complications, Mortality, and Functional Status Among Survivors. Pediatr Crit Care Med. 2018; 19:245–253.

Dannevig I, Solevåg AL, Sonerud T, Saugstad OD, Nakstad B. Brain inflammation induced by severe asphyxia in newborn pigs and the impact of alternative resuscitation strategies on the newborn central nervous system. Pediatr Res. 2013;73:163-70.

Garcia-Hidalgo C, Cheung PY, Solevåg AL, Vento M, O'Reilly M, Saugstad O, Schmölzer GM. A Review of Oxygen Use During Chest Compressions in Newborns-A Meta-Analysis of Animal Data. Front Pediatr. 2018. 18;6:400. PMID: 30619794

Linner R, Werner O, Perez-de-Sa V, Cunha-Goncalves D. Circulatory recovery is as fast with air ventilation as with 100% oxygen after asphyxia-induced cardiac arrest in piglets. Pediatr Res. 2009; 66:391–4.

Marquez AM, Morgan RW, Karlsson M, Ko TS, Landis WP, Mavroudis CD, Starr J. A Randomized, Blinded Trial of 100% Oxygen vs. Room Air During Cardiopulmonary Resuscitation in a Large Animal Model of Pediatric Cardiac Arrest. Circulation. 2018;138:A278 (conference abstract; pending publication).

Solevåg AL, Schmölzer GM, OReilly M, Lu M, Lee T-F, Hornberger LK, Nakstad B. Myocardial perfusion and oxidative stress after 21% vs. 100% oxygen ventilation and uninterrupted chest compressions in severely asphyxiated piglets. Resuscitation. 2016. 106:7–13.

Spindelboeck W, Schindler O, Moser A, Hausler F, Wallner S, Strasser C, Haas J, Gemes G, Prause G: Increasing arterial oxygen partial pressure during cardiopulmonary resuscitation is associated with improved rates of hospital admission. Resuscitation 2013, 84:770–775.

Sutton RM, Reeder RW, Landis WP, Meert KL, Yates AR, Morgan RW; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN). Ventilation Rates and Pediatric In-Hospital Cardiac Arrest Survival Outcomes. Crit Care Med. 2019; 47:1627-1636.

Vereczki V, Martin E, Rosenthal RE, Hof PR, Hoffman GE, Fiskum G. Normoxic vresuscitation after cardiac arrest protects against hippocampal oxidative stress, metabolic dysfunction, and neuronal death. J Cereb Blood Flow Metab. 2006; 26: 821-35. Erratum in: Resuscitation 1994; 27:267.

Walson KH, Tang M, Glumac A, Alexander H, Manole MD, Ma L, Hsia CJ. Normoxic versus hyperoxic resuscitation in pediatric asphyxial cardiac arrest: effects on oxidative stress. Crit Care Med. 2011; 39:335-43.

Zwemer CF, Whitesall SE, D'Alecy LG. Cardiopulmonary-cerebral resuscitation with 100% oxygen exacerbates neurological dysfunction following nine minutes of normothermic cardiac arrest in dogs. Resuscitation. 1994; 27:159-70. Erratum in: Resuscitation 1994; 27:267.

Appendix A: Search Strategies

1. Database: PubMed

Search date: 31st October 2019

Search Strings:

(((((((((((((((Air[MesH] or air[Title/Abstract]) OR Oxygen[MeSH]) OR oxygen*[Title/Abstract] OR O2[Title/Abstract] OR hypoxia[Title/Abstract] OR hypoxaemia[Title/Abstract]) OR hypoxemia[Title/Abstract] OR hyperoxia[Title/Abstract] OR hyperoxia[Title/Abstract] OR hyperoxemia[Title/Abstract] OR hyperoxaemia[Title/Abstract] OR oxygen titration[Title/Abstract] OR saturation[Title/Abstract] OR oximetry[Title/Abstract] OR Ventilation[MeSH]) OR Ventilation[Title/Abstract]) AND ((((((((((((((((((((Heart Arrest[MeSH Terms]) OR heart massage*[Title/Abstract]) OR heart arrest[Title/Abstract]) OR cardiac arrest[Title/Abstract]) OR cardiopulmonary arrest[Title/Abstract]) OR cardiovascular arrest[Title/Abstract]) OR Ventricular Fibrillation[MeSH Terms]) OR ventricular fibrillation[Title/Abstract]) OR asystol*[Title/Abstract]) OR pulseless electrical activity[Title/Abstract]) OR PEA[Title/Abstract]) OR resuscitation[Title/Abstract] OR Cardiopulmonary Resuscitation[MeSH Terms]) OR cardiopulmonary resuscitation[Title/Abstract]) OR life support[Title/Abstract]) OR ACLS[Title/Abstract]) OR Heart Massage[MeSH Terms]) OR heart massage*[Title/Abstract]) OR cardiac massage*[Title/Abstract]) OR chest compression*[Title/Abstract]) OR cardiac compression*[Title/Abstract])) AND ((((((((Child [MeSH Terms]) OR child*[Title/Abstract]) OR Infant[MeSH Terms]) OR infant*[Title/Abstract]) OR Adolescent[MeSH Terms]) OR adolescen*[Title/Abstract]) OR teenage*[Title/Abstract] OR Pediatrics[MeSH] OR pediatric*[Title/Abstract]) OR paediatric* [Title/Abstract]))

2. Database: EMBASE

Search date: 31st October 2019

Search Strings:

(‘Air’/exp or ‘air’:ab,ti OR ‘Oxygen’/exp OR ‘oxygen’:ab,ti OR ‘oxygen*’:ab,ti OR ‘O2’:ab,ti OR ‘hypoxia’:ab,ti OR ‘hypoxaemia’:ab,ti OR ‘hypoxemia’:ab,ti OR ‘hyperoxia’:ab,ti OR ‘hyperoxia’:ab,ti OR ‘hyperoxemia’:ab,ti OR ‘hyperoxaemia’:ab,ti OR ‘Saturation/exp OR ‘saturation’:ab,ti OR ‘Oximetry’/exp OR ‘oximetry’:ab,ti OR ‘oxygen-titration’:ab,ti OR ‘Ventilation’/exp OR ventilation:ab,ti) AND (‘Heart Arrest’/exp OR ‘heart arrest’:ab,ti OR ‘cardiac arrest’:ab,ti OR asystole*:ab,ti OR ‘cardiopulmonary arrest’:ab,ti OR ‘cardiovascular arrest’:ab,ti OR ‘Heart Ventricular Fibrillation’/de OR ‘ventricular fibrillation’:ab,ti OR ‘cardiopulmonary resuscitation’:ab,ti OR CPR:ab,ti OR ‘pulseless electrical activity’:ab,ti OR ‘life support’:ab,ti OR ACLS:ab,ti OR ‘Heart Massage’/de OR ‘heart massage’:ab,ti OR ‘cardiac massage’:ab,ti OR ‘chest compression’:ab,ti OR ‘cardiac compression’:ab,ti OR ‘intra-arrest’:ab,ti]) AND ([‘Child’/exp OR ‘child*’:ab,ti OR ‘Infant’/exp OR ‘infan*’:ab,ti OR ‘Adolescent’/exp OR ‘adolescen*’:ab,ti OR ‘teenage*’:ab,ti OR ‘Preschool’/de OR ‘School’/de OR ‘Pediatrics’/exp OR ‘pediatric*’:ab,ti OR ‘paediatric*’/exp OR ‘paediatric*’:ab,ti]) AND [Embase]/lim

3. Database: Cochrane

Search date: 31st October 2019

Search Strings:

([mh “Air”] or ‘air’:ab,ti OR [mm “Oxygen”] OR ‘oxygen*’:ab,ti OR ‘oxygen*’:ab,ti OR ‘O2’:ab,ti OR ‘hypoxia’:ab,ti OR ‘hypoxaemia’:ab,ti OR ‘hypoxemia’:ab,ti OR ‘hyperoxia’:ab,ti OR ‘hyperoxia’:ab,ti OR ‘hyperoxemia’:ab,ti OR ‘hyperoxaemia’:ab,ti OR ‘Saturation/exp OR ‘saturation’:ab,ti OR ‘Oximetry’/exp OR ‘oximetry’:ab,ti OR ‘oxygen-titration’:ab,ti OR ‘Ventilation’/exp OR ventilation:ab,ti) AND [mh “Heart Arrest”] OR ‘heart arrest’:ab,ti OR ‘cardiac arrest’:ab,ti OR asystol*:ab,ti OR [mm “Heart Ventricular Fibrillation”] OR ‘pulseless electrical activity’:ab,ti OR ‘cardiopulmonary arrest’:ab,ti OR ‘cardiovascular arrest’:ab,ti OR ‘cardiopulmonary resuscitation’:ab,ti OR CPR:ab,ti OR ‘life support’:ab,ti OR ACLS:ab,ti OR [mm “Heart Massage”] OR ‘heart massage’:ab,ti OR ‘cardiac massage’:ab,ti OR ‘chest compression’:ab,ti OR ‘cardiac compression’:ab,ti OR ‘intra-arrest’:ab,ti) AND ([mm “Child”] OR child*:ab,ti OR [mm “Infant”] OR infan*:ab,ti OR [mm “Adolescent”] OR adolescen*:ab,ti OR teenage*:ab,ti OR pediatric*:ab,ti OR paediatric*’:ab,ti])

4. Database: CINAHL

Search date: 31st October 2019

Search Strings:

([mh “Air”] or ‘air’:ab,ti OR [mh “Oxygen”] OR ‘oxygen*’:ab,ti OR ‘oxygen*’:ab,ti OR ‘O2’:ab,ti OR ‘hypoxia’:ab,ti OR ‘hypoxaemia’:ab,ti OR ‘hypoxemia’:ab,ti OR ‘hyperoxia’:ab,ti OR ‘hyperoxia’:ab,ti OR ‘hyperoxemia’:ab,ti OR ‘hyperoxaemia’:ab,ti OR ‘Saturation/exp OR ‘saturation’:ab,ti OR ‘Oximetry’/exp OR ‘oximetry’:ab,ti OR ‘oxygen-titration’:ab,ti OR ‘Ventilation’/exp OR ventilation:ab,ti) AND [mh “Heart Arrest”] OR ‘heart arrest’:ab,ti OR ‘cardiac arrest’:ab,ti OR asystol*:ab,ti OR ‘cardiopulmonary arrest’:ab,ti OR ‘cardiovascular arrest’:ab,ti OR ‘ventricular fibrillation’:ab,ti OR ‘cardiopulmonary resuscitation’:ab,ti OR CPR:ab,ti OR ‘pulseless electrical activity’:ab,ti OR ‘life support’:ab,ti OR ACLS:ab,ti OR [mh “Heart Massage”] OR ‘heart massage’:ab,ti OR ‘cardiac massage’:ab,ti OR ‘chest compression’:ab,ti OR ‘cardiac compression’:ab,ti OR ‘intra-arrest’:ab,ti) AND ([mh “Child”] OR child*:ab,ti OR [mh “Infant”] OR infan*:ab,ti OR [mh “Adolescent”] OR adolescen*:ab,ti OR ‘teenage*’:ab,ti OR [mh “Pediatrics”] OR pediatric*:ab,ti OR paediatric*’:ab,ti])


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