Peripheral Veno-Arterial-Extracorporeal Membrane Oxygenation for Refractory Septic Shock in Children: A Multicenter Review.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is utilized as a rescue therapy in the management of pediatric patients with refractory septic shock. Multiple studies support the use of a central cannulation strategy in these patients. This study aimed to assess the survival of and identify mortality risk factors in pediatric patients supported with peripheral veno-arterial (VA) ECMO in the setting of septic shock. METHODS: We retrospectively reviewed and compared clinical characteristics of 40 pediatric patients supported with peripheral VA ECMO for refractory septic shock, at two tertiary care children's hospitals from 2006 to 2020. Our hypothesis was that peripheral VA ECMO is effective in supporting cardiac function and improving tissue oxygenation in most pediatric patients with refractory septic shock. RESULTS: The overall rate of survival to discharge was 52.5%, comparable to previously reported survival for pediatric sepsis on ECMO. With the exclusion of patients with an oncologic process, the survival rate rose to 62.5%. There was a statistically significant difference in mean pump flow rates within 2 hours of initiation of ECMO between survivors and non-survivors (98 mL/kg/min vs 76 mL/kg/min, P = .050). There was no significant difference between pre-ECMO vasoactive inotropic score (VIS) in survivors and non-survivors. A faster decrease in VIS in the first 24 hours was associated with lower mortality. CONCLUSIONS: From this large case series, we conclude that peripheral VA ECMO is a safe and effective modality to support pediatric patients with refractory septic shock, provided there is establishment of high ECMO pump flows in the first few hours after cannulation and improvement in the VIS.

Routine Neuroimaging: Understanding Brain Injury in Pediatric Extracorporeal Membrane Oxygenation.

OBJECTIVES: This project aims to describe brain injuries on routine neuroimaging in a large single-center neonatal and pediatric cohort supported by extracorporeal membrane oxygenation. The study also aims to examine the association of these injuries with neurocognitive outcomes in survivors and identify laboratory findings associated with neurologic injury. DESIGN: Retrospective observational single-center cohort study. SETTING: Tertiary care PICU. PATIENTS: Pediatric patients with noncardiac indications for extracorporeal membrane oxygenation supported by venoarterial or venovenous extracorporeal membrane oxygenation, with on-extracorporeal membrane oxygenation brain CT or postextracorporeal membrane oxygenation brain CT/MRI. INTERVENTIONS: Extracorporeal membrane oxygenation support. MEASUREMENTS AND MAIN RESULTS: Occurrence of brain injury on CT and MRI was reviewed; injuries were scored. Clinical and laboratory results associated with injury were identified. Survivor neurocognitive outcomes were obtained using the Pediatric Overall Performance Category scale and Pediatric Cerebral Performance Category scale. Of 132 imaged patients, 98 (74%) had radiological evidence of brain injury. Mean injury score was 6.5 (± 3.8). Head ultrasounds and clinician suspicion performed poorly in suspecting the presence of injury. Of 104 respondents to neurodevelopmental assessments, 61 (59%) had normal scores; 12.5%, 17%, and 11.5% had mild, moderate, or severe disability. A neuroimaging score greater than 10 was associated with an unfavorable outcome on the Pediatric Cerebral Performance Category (odds ratio, 3.4; p < 0.01) and Pediatric Overall Performance Category (odds ratio, 1.7; p < 0.05). Ischemic injury correlated with worse neurodevelopmental outcome. Preextracorporeal membrane oxygenation lactate, Vasoactive-Inotropic Scores, transaminitis, elevated bilirubin and creatinine levels, and thrombocytopenia were associated with injury occurrence. CONCLUSIONS: Brain injury is frequent in extracorporeal membrane oxygenation patients, although the majority of survivors have favorable neurocognitive outcomes. More research is needed in order to understand the etiology of such injuries. Head ultrasound and clinician suspicion are not sensitive in detecting extracorporeal membrane oxygenation-related brain injuries. Protocolizing postextracorporeal membrane oxygenation imaging with brain MRI allows the identification of injuries and provision of timely neurocognitive intervention.

Outcomes of Pediatric Extracorporeal Cardiopulmonary Resuscitation: A Systematic Review and Meta-Analysis.

OBJECTIVE: The goal of this work is to provide insight into survival and neurologic outcomes of pediatric patients supported with extracorporeal cardiopulmonary resuscitation. DATA SOURCES: A systematic search of Embase, PubMed, Cochrane, Scopus, Google Scholar, and Web of Science was performed from January 1990 to May 2020. STUDY SELECTION: A comprehensive list of nonregistry studies with pediatric patients managed with extracorporeal cardiopulmonary resuscitation was included. DATA EXTRACTION: Study characteristics and outcome estimates were extracted from each article. DATA SYNTHESIS: Estimates were pooled using random-effects meta-analysis. Differences were estimated using subgroup meta-analysis and meta-regression. The Meta-analyses Of Observational Studies in Epidemiology guideline was followed and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation system. Twenty-eight studies (1,348 patients) were included. There was a steady increase in extracorporeal cardiopulmonary resuscitation occurrence rate from the 1990s until 2020. There were 32, 338, and 1,094 patients' articles published between 1990 and 2000, 2001 and 2010, and 2010 and 2020, respectively. More than 70% were cannulated for a primary cardiac arrest. Pediatric extracorporeal cardiopulmonary resuscitation patients had a 46% (CI 95% = 43-48%; p < 0.01) overall survival rate. The rate of survival with favorable neurologic outcome was 30% (CI 95% = 27-33%; p < 0.01). CONCLUSIONS: The use of extracorporeal cardiopulmonary resuscitation is rapidly expanding, particularly for children with underlying cardiac disease. An overall survival of 46% and favorable neurologic outcomes add credence to this emerging therapy.

EEG is A Predictor of Neuroimaging Abnormalities in Pediatric Extracorporeal Membrane Oxygenation.

The goal of this project was to evaluate if severity of electroencephalogram (EEG) during or shortly after being placed on extracorporeal membrane oxygenation (ECMO) would correlate with neuroimaging abnormalities, and if that could be used as an early indicator of neurologic injury. This was a retrospective chart review spanning November 2009 to May 2018. Patients who had an EEG recording during ECMO or within 48 hours after being decannulated (early group) or within 3 months of being on ECMO (late group) were included if they also had ECMO-related neuroimaging. In the early EEG group, severity of the EEG findings of mild, moderate, and severe EEG correlated to mild, moderate, and severe neuroimaging scores. Patients on venoarterial (VA) ECMO were noted to have higher EEG and neuroimaging severity; this was statistically significant. There was no association in the late EEG group to neuroimaging abnormalities. Our study highlights that EEG severity can be an early predictor for neuroimaging abnormalities that can be identified by computed tomography (CT) and or magnetic resonance imaging (MRI). This can provide guidance for both the medical team and families, allowing for a better understanding of overall prognosis.

Neural Networks to Predict Radiographic Brain Injury in Pediatric Patients Treated with Extracorporeal Membrane Oxygenation.

Brain injury is a significant source of morbidity and mortality for pediatric patients treated with Extracorporeal Membrane Oxygenation (ECMO). Our objective was to utilize neural networks to predict radiographic evidence of brain injury in pediatric ECMO-supported patients and identify specific variables that can be explored for future research. Data from 174 ECMO-supported patients were collected up to 24 h prior to, and for the duration of, the ECMO course. Thirty-five variables were collected, including physiological data, markers of end-organ perfusion, acid-base homeostasis, vasoactive infusions, markers of coagulation, and ECMO-machine factors. The primary outcome was the presence of radiologic evidence of moderate to severe brain injury as established by brain CT or MRI. This information was analyzed by a neural network, and results were compared to a logistic regression model as well as clinician judgement. The neural network model was able to predict brain injury with an Area Under the Curve (AUC) of 0.76, 73% sensitivity, and 80% specificity. Logistic regression had 62% sensitivity and 61% specificity. Clinician judgment had 39% sensitivity and 69% specificity. Sequential feature group masking demonstrated a relatively greater contribution of physiological data and minor contribution of coagulation factors to the model's performance. These findings lay the foundation for further areas of research directions.

Cerebral Hemodynamic Profile in Ischemic and Hemorrhagic Brain Injury Acquired During Pediatric Extracorporeal Membrane Oxygenation.

OBJECTIVES: To describe the cerebral hemodynamic profiles associated with ischemic and hemorrhagic brain injury during neonatal and pediatric extracorporeal membrane oxygenation. DESIGN: A retrospective cohort study. SETTING: Tertiary PICU. PATIENTS: Forty-seven neonatal and pediatric patients (0-15 yr of age) placed on extracorporeal membrane oxygenation from January 2014 to December 2018. MEASUREMENTS AND MAIN RESULTS: Continuous monitoring of mean arterial pressure and cerebral tissue oxygen saturation was conducted through entire extracorporeal membrane oxygenation run. Wavelet analysis was performed to assess changes in cerebral autoregulation and to derive pressure-dependent autoregulation curves based on the mean arterial pressure and cerebral tissue oxygen saturation data. Patients were classified into three brain injury groups: no-injury, ischemic injury, and hemorrhagic injury based on neuroimaging results. No-injury patients (n = 23) had minimal variability in the autoregulation curve over a broad range of blood pressure. Ischemic injury (n = 16) was more common than hemorrhagic injury (n = 8), and the former was associated with increased mortality and morbidity. Ischemic group showed significant abnormalities in cerebral autoregulation in the lower blood pressure range, suggesting pressure-dependent cerebral perfusion. Hemorrhagic group had highest average blood pressure as well as the lowest cerebral tissue oxygenation saturation, suggesting elevated cerebral vascular resistance. Mean heparin dose during extracorporeal membrane oxygenation was lower in both ischemic and hemorrhagic groups compared with the no-injury group. CONCLUSIONS: This study outlines distinct differences in underlying cerebral hemodynamics associated with ischemic and hemorrhagic brain injury acquired during extracorporeal membrane oxygenation. Real-time monitoring of cerebral hemodynamics in patients acquiring brain injury during extracorporeal membrane oxygenation can help optimize their management.