Background
Significant long-term neurologic disability occurs in survivors of pediatric cardiac arrest, primarily due to hypoxic-ischemic brain injury. Postresuscitation care focuses on preventing ...secondary injury and the pathophysiologic cascade that leads to neuronal cell death. These injury processes include reperfusion injury, perturbations in cerebral blood flow, disturbed oxygen metabolism, impaired autoregulation, cerebral edema, and hyperthermia. Postresuscitation care also focuses on early injury stratification to allow clinicians to identify patients who could benefit from neuroprotective interventions in clinical trials and enable targeted therapeutics.
Methods
In this review, we provide an overview of postcardiac arrest pathophysiology, explore the role of neuromonitoring in understanding postcardiac arrest cerebral physiology, and summarize the evidence supporting the use of neuromonitoring devices to guide pediatric postcardiac arrest care. We provide an in-depth review of the neuromonitoring modalities that measure cerebral perfusion, oxygenation, and function, as well as neuroimaging, serum biomarkers, and the implications of targeted temperature management.
Results
For each modality, we provide an in-depth review of its impact on treatment, its ability to stratify hypoxic-ischemic brain injury severity, and its role in neuroprognostication.
Conclusion
Potential therapeutic targets and future directions are discussed, with the hope that multimodality monitoring can shift postarrest care from a one-size-fits-all model to an individualized model that uses cerebrovascular physiology to reduce secondary brain injury, increase accuracy of neuroprognostication, and improve outcomes.
Background The primary objective was to develop a porcine model of prolonged (30 or 60 minutes) pediatric cardiopulmonary resuscitation (CPR) followed by 22- to 24-hour survival with extracorporeal ...life support, and secondarily to evaluate differences in neurologic injury. Methods and Results Ten-kilogram, 4-week-old female piglets were used. First, model development established the technique (n=8). Then, a pilot study was conducted (n=15). After 80% survival was achieved in the final 5 pilot animals, a proof-of-concept randomized study was completed (n=11). Shams (n=6) underwent anesthesia only. Severe neurological injury was determined by a composite score of mitochondrial function, neuropathology, and cerebral metabolism: scale of 0-6 (severe: >3). Among 15 piglets in the pilot study, overall survival was 10 (67%); of the final 5, overall survival was 4 (80%). Eleven piglets were then randomized to 60 (CPR60, n=5) or 30 minutes of CPR (CPR30, n=5); 1 animal was excluded from prerandomization for intra-abdominal hemorrhage (10/11, 91% survival). Three of 5 animals in the CPR60 group had severe neurological injury scores versus 1 of 5 in the CPR30 group (
=0.52). During ECMO, CPR60 animals had lower pH (CPR60: 7.4 IQR 7.4-7.4 versus CPR30: 7.5 IQR 7.4-7.5,
=0.022), higher lactate (CPR60: 6.8 IQR 6.8-11 versus CPR30: 4.2 IQR 4.1-4.3 mmol/L;
=0.012), and higher ICP (CPR60: 19.3 IQR 11.7-29.3 versus CPR30: 7.9 IQR 6.7-9.3 mm Hg;
=0.037). Both groups had greater mitochondrial injury than shams (CPR60:
<0.001; CPR30:
<0.001). CPR60 did not differ from CPR30 in mitochondrial respiration, neuropathology, or cerebral metabolism. Conclusions A pediatric porcine model of extracorporeal cardiopulmonary resuscitation after 60 and 30 minutes of CPR consistently resulted in 24-hour survival with more severe lactic acidosis in the 60-minute cohort.
The objective of this study was to determine the association of the use of extracorporeal cardiopulmonary resuscitation (ECPR) with survival to hospital discharge in pediatric patients with a ...noncardiac illness category. A secondary objective was to report on trends in ECPR usage in this population for 20 years.
Retrospective multicenter cohort study.
Hospitals contributing data to the American Heart Association's Get With The Guidelines-Resuscitation registry between 2000 and 2021.
Children (<18 yr) with noncardiac illness category who received greater than or equal to 30 minutes of cardiopulmonary resuscitation (CPR) for in-hospital cardiac arrest.
None.
Propensity score weighting balanced ECPR and conventional CPR (CCPR) groups on hospital and patient characteristics. Multivariable logistic regression incorporating these scores tested the association of ECPR with survival to discharge. A Bayesian logistic regression model estimated the probability of a positive effect from ECPR. A secondary analysis explored temporal trends in ECPR utilization. Of 875 patients, 159 received ECPR and 716 received CCPR. The median age was 1.0 interquartile range: 0.2-7.0 year. Most patients (597/875; 68%) had a primary diagnosis of respiratory insufficiency. Median CPR duration was 45 35-63 minutes. ECPR use increased over time ( p < 0.001). We did not identify differences in survival to discharge between the ECPR group (21.4%) and the CCPR group (16.2%) in univariable analysis ( p = 0.13) or propensity-weighted multivariable logistic regression (adjusted odds ratio 1.42 95% CI, 0.84-2.40; p = 0.19). The Bayesian model estimated an 85.1% posterior probability of a positive effect of ECPR on survival to discharge.
ECPR usage increased substantially for the last 20 years. We failed to identify a significant association between ECPR and survival to hospital discharge, although a post hoc Bayesian analysis suggested a survival benefit (85% posterior probability).
We analyzed a prospective database of pediatric traumatic brain injury patients to identify predictors of outcome and describe the change in function over time. We hypothesized that neurologic status ...at hospital discharge would not reflect the long-term neurologic recovery state.
This is a descriptive cohort analysis of a single-center prospective database of pediatric traumatic brain injury patients from 2001 to 2012. Functional outcome was assessed at hospital discharge, and the Glasgow Outcome Scale Extended Pediatrics or Glasgow Outcome Scale was assessed on average at 15.8 months after injury.
Children's Medical Center Dallas, a single-center PICU and Level 1 Trauma Center.
Patients, 0-17 years old, with complicated-mild/moderate or severe accidental traumatic brain injury.
Dichotomized long-term outcome was favorable in 217 of 258 patients (84%), 80 of 82 patients (98%) with complicated-mild/moderate injury and 133 of 172 severe patients (77%). In the bivariate analysis, younger age, motor vehicle collision as a mechanism of injury, intracranial pressure monitor placement, cardiopulmonary resuscitation at scene or emergency department, increased hospital length of stay, increased ventilator days (all with p < 0.01) and occurrence of seizures (p = 0.03) were significantly associated with an unfavorable outcome. In multiple regression analysis, younger age (p = 0.03), motor vehicle collision (p = 0.01), cardiopulmonary resuscitation (p < 0.01), and ventilator days (p < 0.01) remained significant. Remarkably, 28 of 60 children (47%) with an unfavorable Glasgow Outcome Scale at hospital discharge improved to a favorable outcome. In severe patients with an unfavorable outcome at hospital discharge, younger age was identified as a risk factor for remaining in an unfavorable condition (p = 0.1).
Despite a poor neurologic status at hospital discharge, many children after traumatic brain injury will significantly improve at long-term assessment. The factors most associated with outcomes were age, cardiopulmonary resuscitation, motor vehicle collision, intracranial pressure placement, days on a ventilator, hospital length of stay, and seizures. The factor most associated with improvement from an unfavorable neurologic status at discharge was being older.
Compare vasopressin to a second dose of epinephrine as rescue therapy after ineffective initial doses of epinephrine in diverse models of pediatric in-hospital cardiac arrest.
67 one- to three-month ...old female swine (10−30kg) in six experimental cohorts from one laboratory received hemodynamic-directed CPR, a resuscitation method where high quality chest compressions are provided and vasopressor administration is titrated to coronary perfusion pressure (CoPP) ≥20mmHg. Vasopressors are given when CoPP is <20mmHg, in sequences of two doses of 0.02mg/kg epinephrine separated by minimum one-minute, then a rescue dose of 0.4 U/kg vasopressin followed by minimum two-minutes. Invasive measurements were used to evaluate and compare the hemodynamic and neurologic effects of each vasopressor dose.
Increases in CoPP and cerebral blood flow (CBF) were greater with vasopressin rescue than epinephrine rescue (CoPP: +8.16 4.35, 12.06 mmHg vs.+5.43 1.56, 9.82 mmHg, p=0.02; CBF: +14.58 -0.05, 38.12 vs.+0.00 -0.77, 18.24 perfusion units (PFU), p=0.005). Twenty animals (30%) failed to achieve CoPP ≥20mmHg after two doses of epinephrine; 9/20 (45%) non-responders achieved CoPP ≥20mmHg after vasopressin. Among all animals, the increase in CBF was greater with vasopressin (+14.58 -0.58, 38.12 vs. 0.00 -0.77, 18.24 PFU, p=0.005).
CoPP and CBF rose significantly more after rescue vasopressin than after rescue epinephrine. Importantly, CBF increased after vasopressin rescue, but not after epinephrine rescue. In the 30% that failed to meet CoPP of 20mmHg after two doses of epinephrine, 45% achieved target CoPP with a single rescue vasopressin dose.
Abstract only
Introduction:
In preclinical models, hemodynamic-directed CPR (HD-CPR) mitigates post-arrest neurofunctional impairment and cerebral mitochondrial dysfunction. We aimed to explore the ...temporal evolution of markers of neurologic injury over five days following cardiac arrest treated with HD-CPR.
Methods:
Pigs (1-month-old) underwent 7min asphyxia, induction of ventricular fibrillation, 10-20min of HD-CPR (goal SBP 90 mmHg, coronary perfusion pressure 20mmHg), randomization to post-ROSC survival duration (24, 48, 72, 96, 120h; n=3 per group) with standardized post-resuscitation care. Plasma neurofilament light (NFL) and glial fibrillary acidic protein (GFAP) were collected at 0, 6, 24, 48, 72, 96, 120h and compared by mixed effects analysis. At terminal endpoints, cerebral cortical tissue was assessed for: mitochondrial electron transport system function; citrate synthase quantification (mitochondrial mass); immunoblot quantification of mitochondrial dynamic proteins (Opa-1, MFN-2, DRP-1, FIS-1); ELISA for 4-HNE and protein carbonyls (oxidative injury); and neuropathologic examination for IBA-1 (microglial activation) and GFAP (reactive astrocytes), all compared via ANOVA.
Results:
All animals had swine cerebral performance category score of 1 (grossly normal) by 24h after injury. Plasma NFL was significantly elevated at 24, 48, 72, 96 (p<0.001) and 120h (p=0.009) compared to baseline. No significant differences were identified between time points for GFAP, mitochondrial measures, or neuropathological outcomes.
Discussion:
Despite grossly normal neurofunctional status, plasma NFL was elevated from baseline at multiple timepoints. No significant temporal differences were identified in other markers of neurologic injury. NFL may be a sensitive marker of mild neurologic injury post-arrest.
Abstract only
Introduction:
Extracorporeal cardiopulmonary resuscitation (ECPR) has been associated with improved outcomes compared to conventional CPR (CCPR) in children with underlying cardiac ...disease. There are limited data on ECPR survival outcomes in the non-cardiac population.
Hypothesis:
ECPR will be associated with improved survival to discharge in children without underlying cardiac disease with prolonged CPR.
Methods:
Retrospective cohort study using the AHA Get With The Guidelines® - Resuscitation registry of children (<18 years) without cardiac disease who received ≥30 minutes of CPR for in-hospital cardiac arrest between 2000-2020. Weighted propensity scores were used to balance ECPR and CCPR groups based on hospital and patient characteristics. Multivariable logistic regression incorporating these scores tested the association of ECPR with survival to discharge. A Bayesian logistic regression model was used to estimate the probability of a positive effect from ECPR. A secondary analysis explored temporal trends in ECPR relative to the index year of 2000.
Results:
Of 875 patients, 159 received ECPR and 716 received CCPR (median age 1 year, primary diagnosis respiratory insufficiency, median CPR duration 45 minutes for full cohort). Survival to discharge was similar between the ECPR group (21.4%) compared to the CCPR group (16.2%) in both the univariable analysis (p= 0.13) and the propensity-weighted multivariable logistic regression (aOR 1.44 CI 0.85-2.44, p= 0.173. The Bayesian model estimated an 85.1% probability of a positive effect of ECPR on survival to discharge. ECPR use increased over time (test for trend p<0.001).
Conclusion:
In children without cardiac disease who required ≥30 minutes of CPR, ECPR usage significantly increased in the last 20 years. Compared to CCPR, ECPR was not associated with a statistically significant increase in survival to discharge. However, a Bayesian model estimated weak evidence of a positive survival effect of ECPR.
Amplitude Spectrum Area (AMSA) is a metric derived from the electrocardiogram (ECG) waveform during ventricular fibrillation (VF). Higher AMSA values have demonstrated strong predictive value for ...successful defibrillation and return of spontaneous circulation (ROSC) during cardiopulmonary resuscitation (CPR). However, there is no consensus on whether AMSA can be reliably estimated during chest compressions. We hypothesize that AMSA is affected by chest compression artifacts, but its predictive value for ROSC is not affected. We tested our hypothesis in a pediatric swine model of cardiac arrest (N=71). For each subject, AMSA was calculated for a pair of adjacent 4-second ECG VF segments prior to defibrillation, one during chest compressions and another during a pause. AMSA calculated during pause was higher than during compressions, both for ROSC (n=46; P<0.001) and No ROSC subjects (n=25; P<0.001). However, the area under the receiver operating characteristic curve for ROSC prediction did not differ between AMSA calculated during pauses and compressions (0.73; p=0.90). Thus, AMSA values were affected by compression artifacts, but ROSC prediction was not impacted. Our finding supports continuous monitoring of AMSA throughout CPR.
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