Post-Cardiac Arrest Care

Post-Cardiac Arrest Temperature Control in Children and Infants

Last Full Review: ILCOR 2020
Last Update: 2021

Recent studies in adults who remain unconscious after return of spontaneous circulation (ROSC) from cardiac arrest have failed to show a benefit with the use of targeted hypothermic temperature control compared with normothermia. Cardiac arrest in children and infants tends to be of hypoxemic origin compared with primary cardiac etiologies in adults, and pediatric cardiac arrest tends to occur in a younger age range. Thus, results of studies of targeted temperature management performed in adults may not apply to children. Are there pediatric-specific studies of post-cardiac arrest hypothermic temperature control to inform guidelines?

 

Evidence Summary

A systematic review of adult and pediatric targeted temperature management post-cardiac arrest with ROSC was completed by the International Liaison Committee on Resuscitation (ILCOR) in 2019 (Buick et al. 2021) with a separate Consensus on Science with Treatment Recommendations (Soar et al. 2019, e826) for children and infants. A weak recommendation was made based on evidence from two randomized controlled trials (RCTs) and eight observational studies, suggesting that for infants and children who remain comatose following ROSC from out-of-hospital cardiac arrest and in-hospital cardiac arrest, targeted temperature management (TTM) be used to maintain a central temperature of 37.5° C (99.5° F) or less. There was inconclusive evidence to support or refute the use of TTM at 32° C to 34° C (89.6° F to 99.5° F) compared with TTM at 36° C to 37.5° C (96.8° F to 99.5° F) or an alternative temperature (Soar et al. 2019, e826).

A 2021 Evidence Update (Scholefield et al. 2021) by ILCOR identified eight new studies, including seven that were secondary analyses of subgroups from the Therapeutic Hypothermia After Pediatric Cardiac Arrest (THAPCA) randomized trial (Moler et al. 2017, 318; Moler et al. 2015, 1898). The secondary analysis data was reported to show no difference between treatment groups of 32° C to 34° (89.6° F to 99.5° F) and 36° C to 37.5° C (96.8° F to 99.5° F) for multiple subgroups. One retrospective cohort study (Magee et al. 2021) found no difference in survival following treatment with induced hypothermia to less than 35° C compared with normothermia (36° C to 37.5° C) [96.8° F to 99.5° F] but did report improved quality of life measures. Treatment recommendations by ILCOR regarding pediatric post-cardiac arrest temperature management remain unchanged other than for a minor wording change from “targeted temperature management” to “active control of temperature” (Scholefield et al. 2021).

Insights and Implications

Results from studies of hypothermic temperature control in pediatric patients with ROSC following cardiac arrest suggest clinical equipoise, highlighting an urgent need for additional well-designed trials. Most cardiac arrest cases included in the TTM1 and TTM2 trials were due to a primary cardiac etiology, and thus results may not be generalizable to all pediatric cardiac arrest populations. In addition, most RCTs to date have not used a rapid cooling time (2 hours post-ROSC) to a targeted temperature. These remain research and knowledge gaps. An approach with active fever control and maintaining normothermia is reasonable for pediatric cardiac arrest patients with ROSC who remain unconscious. The guidelines option to consider the use of hypothermic temperature control for certain pediatric post-cardiac arrest patients who remain unconscious following ROSC reflects clinical equipoise with the potential benefit from hypothermic temperature control in certain pediatric patients and settings. Guidance recommending against prehospital cooling using a rapid infusion of large volume of cold intravenous fluids is informed by ILCOR (Soar et al. 2021) and based on a 2014 trial (Kim et al. 2014, 45) showing increased rates of rearrest and pulmonary edema.

Post-ROSC Blood Pressure Targets After Pediatric Cardiac Arrest

Last Full Review: ILCOR 2025
Last Update: 2024

Hypotension in children and infants with return of spontaneous circulation (ROSC) following cardiac arrest can be due to myocardial dysfunction and ischemia-reperfusion injury, leading to secondary cerebral and myocardial injury and poor outcomes. Following a 2015 International Liaison Committee on Resuscitation (ILCOR) review of interventions to maintain targeted measures of perfusion in infants and children after ROSC (de Caen et al. 2015, S526), it was recommended that for infants and children after ROSC, parenteral fluids and/or inotropes or vasopressors be used to maintain a systolic blood pressure (BP) of at least greater than the 5^th percentile for age. However, the optimal (i.e., target) perfusion endpoints for infants and children with ROSC following cardiac arrest was noted as a knowledge gap. A 2024 systematic review and Consensus on Science with Treatment Recommendations (CoSTR) (Greif et al. 2024, e580) by ILCOR identified evidence supporting a recommendation that a systolic BP greater than the 10^th percentile for age should be the target in infants and children after return of circulation (ROC). Shortly after the 2024 ILCOR systematic review was completed, additional studies were published, triggering an updated systematic review for 2025.

Normative values for blood pressure in children are based on age, sex and height and are available in online tables or apps to assist healthcare professionals with determining the 10th percentile for systolic blood pressure and mean arterial pressure (American Academy of Pediatrics 2004, 555; Banker et al. 2016, 98; Flynn et al. 2017, e20181739; Rosner et al. 2008, 653; Rosner et al. 1993, 871).

 

Evidence Summary

A 2025 ILCOR systematic review and Consensus on Science with Treatment Recommendations (CoSTR) (Nuthall et al. 2024; Scholefield et al.2025, S116) assessed evidence for a specific blood pressure target in infants and children in any setting after ROSC or ROC, compared with no blood pressure target or a different blood pressure target. The final analysis included four nonrandomized observational cohort studies (Topjian et al. 2014, 1518; Topjian et al. 2019, 88; Topjian et al. 2018, 143; Laverriere et al. 2020, 143) that examined the BP targets of a systolic BP greater than the 5^th percentile for age compared with a systolic of the 5^th or less percentile within the first 6 hours post-ROC. One study (Gardner et al. 2023, 388) was included that compared a systolic BP greater than the 10^th percentile with a systolic blood pressure at or less than the 10^th percentile within the first 6 hours after ROC.

For outcomes of survival (Topjian et al. 2014, 1518; Topjian et al. 2018, 143; Topjian et al. 2019, 88; Laverriere et al. 2020, 143) and survival with good neurological outcomes (Topjian et al. 2014, 1518; Laverriere et al. 2020, 143), a benefit was shown from exposure to a systolic BP greater than the 5^th percentile for age when compared with a systolic BP of the 5^th or less percentile (pooled aRR, 1.34; 95% CI, 1.07–1.52; P=0.01; and pooled aRR, 1.30; 95% CI, 1.06–1.60; P=0.01, respectively).

An observational study by Gardner et al. (Gardner et al. 2023, 388) prospectively collected BP data from the first 24 hours following ROC from in-hospital cardiac arrest events enrolled in the ICU-Resuscitation (ICU-RESUS) clinical trial (Sutton et al. 2022, 934). The lowest documented systolic BP and diastolic BP for each patient at 0 to 6 hours and 6 to 12 hours post-ROC were percentile-adjusted for age, sex and height using normative BP data in the healthy pediatric population. Data was used to explore the association of the lowest post-arrest systolic BP and diastolic BP with survival to hospital discharge and survival to discharge with favorable neurological outcome. Statistical analysis and models were used to identify the threshold probability for these outcomes. Thresholds identified from 693 index events with BP data from the first 6 hours post-arrest included a systolic BP above the 10th percentile for age, sex and height. Just over half of the study subjects had their lowest systolic BP above the 10^th percentile threshold. Compared with exposure to a systolic BP at or below the 10^th percentile, a systolic BP above the 10^th percentile was associated with survival to hospital discharge (aRR, 1.21; 95% CI 1.10–1.33) and survival to hospital discharge with favorable neurological outcome (aRR, 1.22; 95% CI, 1.10–1.35) (Gardner et al. 2023, 388). Cut-offs of mean arterial pressure (5^th, 10^th and 25^th percentiles for age) for within 6 hours after ROC were also analyzed for survival outcomes. Compared with an exposure to a mean arterial BP at or below the 10^th percentile, a mean arterial BP above the 10^th percentile was associated with favorable neurological outcome at hospital discharge (aRR, 1.21; 95% CI, 1.05–1.32).

The ILCOR treatment recommendation has been updated to include a mean arterial blood pressure target. A weak recommendation suggests in infants and children post-ROC following an in-hospital or out-of-hospital cardiac arrest that a systolic or mean arterial blood pressure greater than the 10^th percentile for age should be targeted (Nuthall et al. 2024; Scholefield et al.2025, S116).

Insights and Implications

No randomized controlled trials have compared two treatment approaches or two BP targets (such as a systolic BP greater than the 5^th percentile versus a systolic BP greater than the 10^th percentile) after cardiac arrest and ROSC, and it was not statistically possible to compare the two treatment targets in the included studies. In discussion of the evidence-to-decision framework for the 2025 systematic review, the ILCOR Pediatric Task Force assessed the overlap between systolic blood pressure thresholds below the 5th and 10th percentiles in children. Due to statistical limitations, a meta-regression to compare these two targets was not feasible. The task force concluded that the less than 10th percentile group encompasses the less than 5th percentile group. Given the low certainty of evidence, they recommended targeting a systolic BP above the 10th percentile to avoid the 5th to 10th percentile range, which has been associated with worse outcomes in pediatric patients, as highlighted in Gardner et al. (Gardner et al. 2023, 388).​

Oxygen and Carbon Dioxide Target Levels 

Last Full Review: ILCOR 2020

A systematic review of a ventilation strategy aimed at specific oxygen and carbon dioxide target levels in unresponsive adults and children with sustained return of spontaneous circulation (ROSC) after cardiac arrest in any setting was performed by the International Liaison Committee on Resuscitation (ILCOR) in 2020 (Holmberg et al. 2020, 107). This corresponded to work done by the American Red Cross Scientific Advisory Council in prior years. 

 

Evidence Summary 

Evidence from the pediatric literature was used to inform this Consensus on Science with Treatment Recommendations (Maconochie et al. 2020, S140). No pediatric randomized controlled trials were identified. Observational studies enrolling 618 children were included; all were judged to be at serious risk of bias and provided evidence of very low certainty (Del Castillo et al. 2012, 1456; Bennett et al. 2013, 1534; van Zellem et al. 2015, 150). One study (Bennett et al. 2013, 1534) with 153 pediatric ROSC patients in any setting found no increase in survival to hospital discharge with good neurologic outcome from hyperoxemia compared with no hyperoxemia. Unadjusted analysis of data (Holmberg et al. 2020, 107) from a study of 164 pediatric patients with ROSC after in-hospital cardiac arrest reported no benefit from hyperoxemia compared with normoxemia for survival to hospital discharge (Del Castillo et al. 2012, 1456). A second study evaluating survival to hospital discharge in 200 pediatric patients with ROSC after cardiac arrest showed no association between a post-ROSC partial pressure of oxygen greater than 200 mmHg and the outcome (van Zellem et al. 2015, 150). A registry-based study (Ferguson, Durward, and Tibby 2012, 335) reported an association between hyperoxemia and higher mortality compared with normoxemia but was deemed at critical risk of bias (Maconochie et al. 2020, S140).

For carbon dioxide targets, two observational studies were included in the 2020 systematic review, (Holmberg et al. 2020, 107) with one (Del Castillo et al. 2012, 1456) showing both hypocapnia after ROSC and hypercapnia after ROSC being associated with hospital mortality. The second study reported an association between hospital mortality and both hypocapnia and hypercapnia 1 hour after ROSC compared with normocapnia (Lopez-Herce et al. 2014, 607). 

A weak recommendation by ILCOR suggests that rescuers measure the partial pressure of oxygen in the arterial blood (PaO₂) after ROSC and target a value appropriate to the specific patient condition. In the absence of specific patient data, it is suggested that rescuers target normoxemia after ROSC. Targeting an oxygen saturation of 94% to 99% with pulse oximetry may be a reasonable alternative to measuring PaO₂ and titrating oxygen when feasible to achieve normoxia (Maconochie et al. 2020, S140). 

It is also suggested by ILCOR that rescuers measure the partial pressure of carbon dioxide in arterial blood (PaCO₂) after ROSC and target normocapnia and consider adjustments to the target PaCO₂ for specific patient populations where normocapnia may not be desirable (such as chronic lung disease with chronic hypercapnia or congenital heart disease with single ventricle) (Maconochie et al. 2020, S140).

Insights and Implications 

The targeting of normoxemia post-ROSC has not been studied in the pediatric prehospital setting, and the ILCOR review commented on the risk of inadvertent hypoxemia from overzealous weaning of oxygen and risks of hypoxemia versus uncertain risks of hyperoxia. 

Post-Cardiac Arrest Seizure Prophylaxis or Treatment

Last Full Review: ILCOR 2024

​​Cardiac arrest is uncommon in children and has a low survival rate, with a significant chance for neurological injury and effects on subsequent neurodevelopment. Seizures or epileptiform activity on electroencephalograms (EEGs) have been reported in up to 47% of comatose patients in the post-cardiac arrest period and are manifestations of post-cardiac arrest hypoxic-ischemic brain injury (Abend et al. 2009, 1931).

A 2024 International Liaison Committee on Resuscitation (ILCOR) systematic review and Consensus on Science with Treatment Recommendations (CoSTR) (Nicholson et al. 2024) was undertaken to investigate the effects of prophylactic anti-seizure medication and treatment of seizures on outcomes of pediatric patients following cardiac arrest.

 

Evidence Summary 

A 2024 ILCOR systematic review and CoSTR (Nicholson et al. 2024; Scholefield et al. 2024; Greif et al. 2024) assessed the effect of prophylaxis and treatment of seizures on survival and neurological and functional outcomes for both adult and pediatric patients with cardiac arrest and return of spontaneous circulation (ROSC). Findings from the adult patient arm of this review can be found in the American Red Cross Healthcare Guidelines for Advanced Life Support: Post-Cardiac Arrest Seizure Prophylaxis or Treatment. 

For the assessment of prophylactic anti-seizure medication on survival with favorable neurological outcome at discharge or 30 days or longer, no randomized controlled trials (RCTs) or nonrandomized comparative studies were identified that included pediatric patients. Indirect evidence from adult patients was considered in this ILCOR review (Brain Resuscitation Clinical Trial 1986, 397; Longstreth et al. 2002, 506; Monsalve et al. 1987, 244). 

One RCT failed to show a benefit from prophylactic anti-seizure medication (thiopentone versus standard care) in 262 patients for survival with good neurological outcome at 12 months (Brain Resuscitation Clinical Trial 1986, 397). A second RCT found no difference from treatment with magnesium, diazepam, or combined treatment with magnesium and diazepam versus placebo for survival with good neurological outcome at 3 months (Longstreth et al. 2002, 506). A nonrandomized prospective trial with historical controls reported no improvement in neurological outcome at hospital discharge with thiopentone compared with standard care (Monsalve et al. 1987, 244).

For the review of seizure treatment post-cardiac arrest, no RCTs or non-RCTs were identified that included pediatric patients and the critical outcome of survival with favorable neurological outcome at discharge. Indirect evidence from studies of adult patients included one randomized study (Ruijter et al. 2022, 724) of 172 patients. The trial compared standard care plus administration of anti-seizure medications versus standard care alone for suppressing rhythmic and generalized periodic EEG activity detected on continuous EEG monitoring for at least 48 consecutive hours. A benefit was not shown with anti-seizure medication for outcomes of survival with favorable neurological outcome at 3 months or for survival. While not an outcome considered in the ILCOR review, complete suppression of rhythmic and periodic EEG activity for 48 consecutive hours occurred in 49/88 patients (56%) in the anti-seizure medication group and in 2/83 patients (2%) in the standard care group.

The ILCOR review (Scholefield et al. 2024; Greif et al. 2024) concluded that there is insufficient evidence to make a treatment recommendation for or against the use of prophylactic anti-seizure medication in children post-cardiac arrest. For anti-seizure prophylaxis, ILCOR made a good practice statement suggesting against the routine use of prophylactic anti-seizure medication in children post-cardiac arrest.

The ILCOR review also concludes that there is insufficient evidence to make a treatment recommendation for or against the treatment of seizures in children post-cardiac arrest. For seizure treatment, ILCOR made a good practice statement suggesting that it is reasonable to treat seizures in children with ROSC following cardiac arrest.

Insights and Implications

In making the good practice statements, the ILCOR CoSTR authors (Scholefield et al. 2024; Greif et al. 2024) considered the lack of direct evidence in children, the indirect evidence from adult cardiac arrest patients that failed to show a benefit from prophylactic anti-seizure medications, and evidence that prophylactic anti-seizure medication in other forms of acute brain injury is not associated with improved long-term outcomes. Newer anti-seizure medications have not been studied for prophylaxis in children post-ROSC and may have fewer side effects or better efficacy. 

For treatment of seizures in children who are post-ROSC, the authors considered that a high seizure burden in children is associated with poor neurological outcomes and that anti-seizure medications can reduce seizures in children with status epilepticus. Lastly, there was insufficient evidence for the authors to suggest for or against treatment of rhythmic and periodic EEG pattern in children post-cardiac arrest. There are many knowledge gaps related to this topic and much more research is needed.