PLS 4180 Post-ROSC Ventilation and Oxygenation - SyR

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 declared.

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: J del Castillo was a Task Force member co-investigator on included studies and therefore excluded from study selection, data abstraction and risk of bias assessment. No members of the writing group have any financial conflicts of interest.

CoSTR Citation

Rossano J, Ambunda E, Bansal A, Christoff A, del Castillo J, Gray J, Katzenschlager S, Kleinman M, Kurosawa H, Morgan R, Morrison L, Myburgh M, Nuthall G, Raymond T, Rech L, Schexnayder S, Thiagarajan R, Tiwari L, Topjian A, Acworth J, Scholefield B, on behalf of the International Liaison Committee on Resuscitation Pediatric Life Support Task Force. Ventilation and Oxygenation after Pediatric Cardiac Arrest: A Systematic Review. Available from: http://ilcor.org

Methodological Preamble Background

The continuous evidence evaluation process for the production of Consensus on Science with Treatment Recommendations (CoSTR) started with a systematic review of basic life support (Rossano 2024, Prospero Registration Number: CRD42024597802) conducted by the Pediatric Life Support Task Force. Evidence for pediatric literature was sought and considered. Additional scientific literature was published after the completion of the systematic review and identified by the Pediatric Task Force and is described before the justifications and evidence to decision highlights section of this CoSTR. These data were taken into account when formulating the Treatment Recommendations.

Systematic Review

Rossano J, Ambunda E, Bansal A, Christoff A, del Castillo J, Gray J, Katzenschlager S, Kleinman M, Kurosawa H, Morgan R, Morrison L, Myburgh M, Nuthall G, Raymond T, Rech L, Schexnayder S, Thiagarajan R, Tiwari L, Topjian A, Acworth J, Scholefield B, on behalf of the International Liaison Committee on Resuscitation Pediatric Life Support Task Force. Ventilation and Oxygenation after Pediatric Cardiac Arrest: A Systematic Review (Pending)

PICOST

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

PROSPERO Registration CRD42024597802

**NOTE FOR RISK OF BIAS: Risk of bias (RoB) was assessed using the Newcastle Ottawa Scale and was deemed to be serious for all studies. In most cases, bias was assessed per comparison rather than per outcome, since there were no meaningful differences in bias across outcomes. In cases where differences in risk of bias existed between outcomes, this was noted.

Consensus on Science

There were seven studies identified in this updated Task Force led systematic review, including the three pediatric studies that were included in the 2019 ILCOR systematic review. There were no prospective pediatric trials, randomized or otherwise, of any specific intervention or targets of oxygenation or ventilation strategy defined as carbon dioxide levels. All of the studies were observational studies, of which 5 were retrospective 2-5 and 2 were prospective. 6,7 The two prospective studies were multi-center observational studies, and one was embedded within a prospective trial.6,7 There was substantial heterogeneity in the study designs, definitions of oxygenation and ventilation categories, and exposure to oxygenation and ventilation categories that precluded combining results for a meta-analysis.

Oxygenation Targets (IHCA and OHCA):

For the critically important outcome of survival to hospital discharge, we identified very low certainty evidence (downgraded for serious risk of bias, indirectness, and imprecision from two prospective studies6,7 and five retrospective studies.2-5,8 One prospective observational study that included 223 children with an in-hospital cardiac arrest found no association with hypoxia, defined as a PaO2 < 60 mmHg on blood gas analysis or PaO2/FiO2 < 200, or hyperoxia, defined as a PaO2 ³ 300 mmHg on blood gas analysis or PaO2/FiO2 > 300, on survival to hospital discharge on blood gas analysis after ROC and 24 hours later.6 The other prospective study enrolled 284 patients with in-hospital cardiac arrest and found hypoxia, defined as a lowest PaO2 < 60 mmHg in the first 24 hours post-arrest, was associated with lower survival to hospital discharge (RR 0.71, 95% CI 0.58 to 0.87).7

None of the other 5 retrospective studies found an overall association for oxygenation targets with survival to hospital discharge.2-5,8 One single-center study included 200 patients with either an out-of-hospital or in-hospital cardiac arrest and found no association of oxygenation and hospital survival to hospital discharge based on minimal PaO2, maximum PaO2, or the area under of the curve for PaO2 values in the first 24 hours after cardiac arrest.3 A subgroup analysis of this study that included patients who underwent mild therapeutic hypothermia (n=58, 29% of total cohort) found that higher cumulative PaO2 levels in 0-24 hours (OR 0.916, 95% CI 0.843 to 0.995) and 6-24 hours after cardiac arrest (OR 0.882, 95% CI 0.792 to 0.981) were associated with improved survival to hospital discharge. Another retrospective study of 15 hospitals included 195 patients who suffered an in-hospital or out-of-hospital or in-hospital cardiac arrest.2 In this study, hypoxia was defined as a PaO2 < 50 mmHg and hyperoxia as PaO2 > 200 mmHg during the first six hours after cardiac arrest and neither were associated with oxygenation and survival to hospital discharge. A single-center, retrospective study of 187 patients with an in-hospital cardiac arrest assessed hyperoxia, defined as having at least one PaO2 level > 200 mmHg in the first 24 hours after a cardiac arrest, and found no association with hyperoxia and survival to hospital discharge (adjusted OR 1.1, 95% CI 0.2 to 2.1).4 A multi-center, retrospective study assessed PaO2 levels on admission to the pediatric intensive care unit (PICU) and included 1500 patients who suffered a cardiac arrest prior to PICU admission and found no association with PaO2 levels on admission post arrest and survival to hospital discharge.8 A multi-center retrospective study that included 292 children from five hospitals who suffered an in-hospital or out-of-hospital cardiac arrest found no association of with PaO2 and survival to hospital discharge based on minimal PaO2, maximum PaO2, or the area under of the curve for PaO2 values in the first 24 hours after cardiac arrest.5

For the critically important outcome of survival to hospital discharge with favorable neurological outcome, we identified very low certainty evidence (downgraded for serious risk of bias, indirectness, and imprecision) from one prospective7 and 3 retrospective studies.2,4,5 The prospective study enrolled 284 patients with in-hospital cardiac arrest and found hypoxemia, defined as lowest PaO2 < 60 mmHg in the first 24 hours post-arrest, was associated with lower survival to hospital discharge with favorable neurologic outcome (RR 0.67, 95% CI 0.52 to 0.85)7. None of the other 3 retrospective studies found an overall association for oxygenation targets with survival to hospital discharge with favorable neurological outcome.2,4,5 A retrospective study of 15 hospitals included 195 patients who suffered an in-hospital or out-of-hospital cardiac arrest.2 In this study, hypoxia was defined as a PaO2 < 50 mmHg and hyperoxia as a PaO2 > 200 mmHg during the first six hours after cardiac arrest and neither was associated with survival to hospital discharge with favorable neurologic outcome. This finding was confirmed on multivariable analysis (adjusted OR 1.2, 95% CI 0.5 to 2.8).4 A multi-center retrospective study that included 292 children from five hospitals who suffered an in-hospital or out-of-hospital cardiac arrest found no association with PaO2 and survival to hospital discharge with favorable neurologic outcome based on minimal PaO2, maximum PaO2, or the area under the curve for PaO2 values in the first 24 hours after cardiac arrest.5

Ventilation strategy was defined as Carbon Dioxide Targets post ROC (IHCA and OHCA):

For the critically important outcome of survival to hospital discharge, we identified very low certainty evidence (downgraded for serious risk of bias, indirectness, and imprecision) from two prospective studies6,7 and two retrospective studies.2,5 One prospective observational study included 223 children with an in-hospital cardiac arrest, defined hypocapnia as PaCO2 < 30 mmHg and hypercapnia as a PaCO2 > 50 mmHg, and found that both hypocapnia (OR 2.71, 95% CI 1.04 – 7.05; p=0.04) and hypercapnia (OR 3.27, 95% CI 1.62 – 6.61; p=0.001) measured after ROC were associated with lower hospital survival; however, PaCO2 values measured at 24 hours post ROC were not associated with hospital survival.6 The other prospective study enrolled 284 patients with in-hospital cardiac arrest and found that hypercapnia, defined as the highest PaCO2 value ³ 50 mmHg in the first 24 hours post-arrest , was associated with lower survival to hospital discharge compared to the normocapnia group (aRR 0.74, 95% CI 0.64 – 0.84).7 Neither of the other two retrospective studies found an overall association of carbon dioxide targets with survival to hospital discharge.2,5 A retrospective study of 15 hospitals included 195 patients who suffered an in-hospital or out-of-hospital cardiac arrest, defined hypocapnia as PaCO2 < 30 mmHg and hypercapnia as a PaCO2 > 50 mmHg and found no association with ventilation and survival to hospital discharge.2 A multi-center retrospective study that included 292 children from five hospitals who suffered an in-hospital or out-of-hospital cardiac arrest found no association with PaCO2 and survival to hospital discharge based on minimal PaCO2, maximum PaCO2, or the area under the curve for PaCO2 values in the first 24 hours after cardiac arrest.5 In a subgroup analysis of infants (< 1 year old), higher cumulative PaCO2 levels were associated with a decreased likelihood of hospital survival (OR 0.80, 95 % CI 0.64 –0.99).

For the critically important outcome of survival to hospital discharge with favorable neurologic outcome, we identified very low certainty evidence (downgraded for serious risk of bias, indirectness, and imprecision) from one prospective study7 and two retrospective studies.2,5 The prospective study enrolled 284 patients with in-hospital cardiac arrest and found that hypercapnia, defined as the highest PaCO2 value ³ 50 mmHg in the first 24 hours post-cardiac arrest was associated with a decreased likelihood of favorable neurologic outcome at hospital discharge (RR 0.74, 95% CI 0.63-0.85).7 Neither of the other two retrospective studies found an overall association for carbon dioxide targets with survival to hospital discharge with favorable neurological outcome.2,5

Treatment Recommendation or Good Practice Statement

No Treatment recommendation

The available evidence was insufficient to make a treatment recommendation for a specific oxygenation or ventilation target in infants and children following return of spontaneous circulation after cardiac arrest. The evidence was observational, heterogeneous, and of very low certainty, with no pediatric trials comparing target-directed strategies.

The prior TR from 2020 has been withdrawn for lack of evidence.

Pediatric Treatment Recommendations from 2020 COSTR:

We suggest that rescuers measure PaO2 after ROSC and target a value appropriate to the specific patient condition. In the absence of specific patient data, we suggest rescuers target normoxemia after ROSC (weak recommendation, very-low-quality evidence). Given the availability of continuous pulse oximetry, targeting an oxygen saturation of 94-99% may be a reasonable alternative to measuring PaO2 and titrating oxygen when feasible to achieve normoxia.

We suggest that rescuers measure PaCO2 after ROSC and target normocapnia (weak recommendation, very-low-certainty evidence). Consider adjustments to the target paCO2 for specific patient populations where normocapnia may not desirable (e.g. chronic lung disease with chronic hypercapnia, congenital heart disease with single ventricle physiology, increased intracranial pressure with impending herniation)  

Good Practice Statement

In infants and children with return of spontaneous circulation after cardiac arrest, oxygenation and ventilation should be measured as soon as practicable and reassessed frequently. (Good Practice Statement)

Inspired oxygen and ventilation should be titrated to normoxia and normocapnia and individualized according to the child's underlying physiology and clinical condition. Until oxygenation can be measured reliably, use 100% inspired oxygen following return of spontaneous circulation. (Implementation Remark)

Interpret PaCO₂ in the context of pH, temperature, end-tidal carbon dioxide, hemodynamic status, ventilatory support, and the child’s underlying physiology. End-tidal carbon dioxide should not be assumed to be equivalent to arterial PaCO₂. (Implementation Remark)

Justification and Evidence to Decision Framework Highlights

During cardiac arrest, cerebral blood flow and oxygen delivery are markedly reduced, even with high-quality cardiopulmonary resuscitation. Although 100% inspired oxygen is used during resuscitation to minimize further hypoxic-ischemic injury, the optimal oxygenation and ventilation targets after return of spontaneous circulation remain uncertain.

No pediatric randomized or prospective interventional trials comparing specific post-resuscitation oxygenation or ventilation targets were identified. The included studies were observational, clinically heterogeneous, and at serious risk of bias. Differences in populations, timing of measurements, exposure definitions, physiological thresholds, and outcome measurement prevented meaningful pooling. The resulting evidence was of very low certainty and was insufficient to support a treatment recommendation for a specific SpO₂, PaO₂, or PaCO₂ target.

Some prospective observational evidence associated hypoxia, hypercapnia, and, in one study, hypocapnia with worse outcomes. These findings were inconsistent across studies and do not establish that targeting a particular numerical range improves patient outcomes.

The good practice statement was therefore framed around the essential clinical practices of reliable measurement and repeated reassessment rather than the comparative superiority of specific numerical targets. The Task Force provided implementation remarks to support this good practice statement.

Other Task Force discussion included:

• Once reliable measurements are available, promptly titrate inspired oxygen. For most infants and children without abnormal baseline oxygenation, an SpO₂ of 94–98% or a PaO₂ of approximately 75–100 mmHg may be used as an operational target for normoxia.
• Measure PaCO₂ as soon as practicable after return of spontaneous circulation. For most infants and children, normocapnia may be used as the initial operational target while avoiding marked hypocapnia and hypercapnia.
• Individualize oxygenation and PaCO₂ targets where usual population ranges may be inappropriate, including in children with cyanotic congenital heart disease with systemic-to-pulmonary shunts or superior cavopulmonary connections, chronic hypercapnia, or specific neurocritical care indications.
• Interpret pulse oximetry cautiously when signal quality is poor, peripheral perfusion is reduced, or SpO₂ may overestimate arterial oxygen saturation.
• These numerical ranges are operational targets for most infants and children and should not be interpreted as evidence that they are superior to all reasonable alternative targets.

In its Evidence to Decision assessment, the Task Force judged that:  

• Oxygenation and ventilation are important and immediately modifiable components of post-resuscitation care.
• The expected benefits of identifying and correcting clinically important physiological abnormalities substantially outweigh the burdens and potential harms of monitoring and treatment adjustment.
• The principal risks arise from unreliable measurements, isolated results, and rigid application of population targets to children with abnormal underlying physiology.
• Monitoring and individualized physiological management are acceptable and generally feasible, although access to arterial blood gas measurement may vary.
• Equity considerations include unequal access to blood gas analysis and the potential for pulse oximetry to provide unreliable measurements or overestimate arterial oxygen saturation.
• Failure to measure oxygenation and ventilation, or failure to respond to clinically important abnormalities, was considered an inappropriate alternative.
• A systematic review of monitoring compared with deliberate non-monitoring would be a poor use of resources. Comparative studies of specific oxygenation and ventilation targets remain necessary.

The numerical ranges are therefore presented as implementation remarks representing pragmatic initial targets for most children, rather than as independently graded treatment recommendations.

Knowledge Gaps

• No pediatric randomized or prospective interventional trials have compared specific post-resuscitation oxygenation or ventilation targets.
• The optimal SpO₂, PaO₂, and PaCO₂ targets after pediatric cardiac arrest remain unknown.
• The optimal timing and rate of inspired oxygen reduction after return of spontaneous circulation are uncertain, particularly in prehospital and emergency care.
• The clinical effects of severity, duration, variability, and cumulative burden of hypoxia, hyperoxia, hypocapnia, and hypercapnia require further study.
• The accuracy and clinical consequences of relying on pulse oximetry and end-tidal carbon dioxide after pediatric cardiac arrest require further evaluation.
• It is uncertain whether targets should differ according to age, arrest location, arrest etiology, duration of resuscitation, severity of post-cardiac arrest syndrome, or the presence of hypoxic-ischemic brain injury.
• Specific targets require evaluation in children with congenital heart disease, abnormal baseline oxygen saturation, chronic lung disease, pulmonary hypertension, chronic hypercapnia, raised intracranial pressure, or extracorporeal support.
• Future studies should compare protocolized physiological targets rather than associations based on isolated blood gas measurements.
• Future studies should report treatment-related adverse effects and patient-important outcomes, including survival, neurological and functional recovery, neurodevelopment, and health-related quality of life at longer-term follow-up.
• Adequately powered, multicenter pediatric trials comparing clearly defined oxygenation and ventilation strategies are needed.

Evidence to Decision (EtD) Tables

To be added.

References

​​1. Topjian AA, Scholefield BR, Pinto NP, Fink EL, Buysse CMP, Haywood K, Maconochie I, Nadkarni VM, de Caen A, Escalante-Kanashiro R, et al. P-COSCA (Pediatric Core Outcome Set for Cardiac Arrest) in Children: An Advisory Statement From the International Liaison Committee on Resuscitation. Circulation. 2020;142:e246–e261. doi: 10.1161/CIR.0000000000000911

​2. Bennett KS, Clark AE, Meert KL, Topjian AA, Schleien CL, Shaffner DH, Dean JM, Moler FW, Pediatric Emergency Care Medicine Applied Research N. Early oxygenation and ventilation measurements after pediatric cardiac arrest: lack of association with outcome. Crit Care Med. 2013;41:1534–1542. doi: 10.1097/CCM.0b013e318287f54c

​3. van Zellem L, de Jonge R, van Rosmalen J, Reiss I, Tibboel D, Buysse C. High cumulative oxygen levels are associated with improved survival of children treated with mild therapeutic hypothermia after cardiac arrest. Resuscitation. 2015;90:150–157. doi: 10.1016/j.resuscitation.2014.12.013

​4. Barreto JA, Weiss NS, Nielsen KR, Farris R, Roberts JS. Hyperoxia after pediatric cardiac arrest: Association with survival and neurological outcomes. Resuscitation. 2022;171:8–14. doi: https://dx.doi.org/10.1016/j.resuscitation.2021.12.003

​5. Albrecht M, de Jonge RCJ, Del Castillo J, Christoff A, De Hoog M, Je S, Nadkarni VM, Niles DE, Tegg O, Wellnitz K, et al. Association of cumulative oxygen and carbon dioxide levels with neurologic outcome after pediatric cardiac arrest resuscitation: A multicenter cohort study. Resusc Plus. 2024;20:100804. doi: 10.1016/j.resplu.2024.100804

​6. Del Castillo J, Lopez-Herce J, Matamoros M, Canadas S, Rodriguez-Calvo A, Cechetti C, Rodriguez-Nunez A, Alvarez AC, Iberoamerican Pediatric Cardiac Arrest Study Network R. Hyperoxia, hypocapnia and hypercapnia as outcome factors after cardiac arrest in children. Resuscitation. 2012;83:1456–1461. doi: 10.1016/j.resuscitation.2012.07.019

​7. Frazier AH, Topjian AA, Reeder RW, Morgan RW, Fink EL, Franzon D, Graham K, Harding ML, Mourani PM, Nadkarni VM, et al. Association of Pediatric Postcardiac Arrest Ventilation and Oxygenation with Survival Outcomes [published correction appears in Comment in: Ann Am Thorac Soc. 2024 Jun;21(6):856-857. doi: 10.1513/AnnalsATS.202404-339ED PMID: 38819137 [https://www.ncbi.nlm.nih.gov/pubmed/38819137]]. Annals of the American Thoracic Society. 2024;21:895–906. doi: https://dx.doi.org/10.1513/AnnalsATS.202311-948OC

​8. Holton C, Lee BR, Escobar H, Benton T, Bauer P. Admission Pa o2 and Mortality Among PICU Patients and Select Diagnostic Subgroups. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2023;24:e362–e371. doi: https://dx.doi.org/10.1097/PCC.0000000000003247

​9. Dewidar O, Singletary EM, Morrison LJ, Schunemann HJ, Lang E, Carlson J, Morley PT, Rabi Y, Committee ISA. ILCOR's refined approach for developing good practice statements: A 2026 update. Resuscitation. 2026:111325. doi: 10.1016/j.resuscitation.2026.111325​