Early Changes in Arterial Partial Pressure of Carbon Dioxide and Blood Pressure After Starting Extracorporeal Membrane Oxygenation in Children: Extracorporeal Life Support Organization Database Study of Neurologic Complications.

OBJECTIVE: Neurologic complications in pediatric patients supported by extracorporeal membrane oxygenation (ECMO) are common and lead to morbidity and mortality; however, few modifiable factors are known. DESIGN: Retrospective study of the Extracorporeal Life Support Organization registry (2010-2019). SETTING: Multicenter international database. PATIENTS: Pediatric patients receiving ECMO (2010-2019) for all indications and any mode of support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We investigated if early relative change in Pa co2 or mean arterial blood pressure (MAP) soon after starting ECMO was associated with neurologic complications. The primary outcome of neurologic complications was defined as a report of seizures, central nervous system infarction or hemorrhage, or brain death. All-cause mortality (including brain death) was used as a secondary outcome.Out of 7,270 patients, 15.6% had neurologic complications. Neurologic complications increased when the relative Pa co2 decreased by greater than 50% (18.4%) or 30-50% (16.5%) versus those who had a minimal change (13.9%, p < 0.01 and p = 0.046). When the relative MAP increased greater than 50%, the rate of neurologic complications was 16.9% versus 13.1% those with minimal change ( p = 0.007). In a multivariable model adjusting for confounders, a relative decrease in Pa co2 greater than 30% was independently associated with greater odds of neurologic complication (odds ratio [OR], 1.25; 95% CI, 1.07-1.46; p = 0.005). Within this group, with a relative decrease in Pa co2 greater than 30%, the effects of increased relative MAP increased neurologic complications (0.05% per BP Percentile; 95% CI, 0.001-0.11; p = 0.05). CONCLUSIONS: In pediatric patients, a large decrease in Pa co2 and increase in MAP following ECMO initiation are both associated with neurologic complications. Future research focusing on managing these issues carefully soon after ECMO deployment can potentially help to reduce neurologic complications.

High Hemoglobin Is an Independent Risk Factor for the Development of Hemolysis During Pediatric Extracorporeal Life Support.

OBJECTIVE: To evaluate risk factors for hemolysis in pediatric extracorporeal life support. DESIGN: Retrospective, single-center study. SETTING: Pediatric intensive care unit. PATIENTS: Two hundred thirty-six children who received extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Risk factors for hemolysis were retrospectively analyzed from a single center in a total of 236 neonatal and pediatric patients who received extracorporeal membrane oxygenation support (ECMO). There was no difference in the incidence of hemolysis between centrifugal (127 patients) and roller head (109 patients) pump type or between venoarterial and venovenous ECMO. High hemoglobin (Hb) was found to be an independent risk factor for hemolysis in both pump types. The Hb level >12 g/dL was significant in the roller group and the Hb level >13 g/dL was significant in the centrifugal group for the development of hemolysis for the cumulative ECMO run. The presence of high Hb levels on any given day increased the risk of hemolysis for that day of the ECMO run regardless of ECMO pump type. Higher revolutions per minute (RPMs) and higher inlet pressures on any given day increased the risk for the development of hemolysis in the centrifugal pump. Lower inlet venous pressures and RPMs were not associated with hemolysis in the roller group. CONCLUSIONS: An Hb level greater than 13 g/dL was associated with an increased risk of hemolysis, and a high Hb on a given day was associated with a significantly higher risk of hemolysis on the same day. Higher RPMs and lower inlet venous pressures were associated with an increased risk of hemolysis in the centrifugal pump only.

Impairment of cerebral autoregulation in pediatric extracorporeal membrane oxygenation associated with neuroimaging abnormalities.

Extracorporeal membrane oxygenation (ECMO) is a life-supporting therapy for critically ill patients with severe respiratory and/or cardiovascular failure. Cerebrovascular impairment can result in hemorrhagic and ischemic complications commonly seen in the patients supported on ECMO. We investigated the degree of cerebral autoregulation impairment during ECMO as well as whether it is predictive of neuroimaging abnormalities. Spontaneous fluctuations of mean arterial pressure (MAP) and cerebral tissue oxygen saturation ([Formula: see text]) were continuously measured during the ECMO run. The dynamic relationship between the MAP and [Formula: see text] fluctuations was assessed based on wavelet transform coherence (WTC). Neuroimaging was conducted during and/or after ECMO as standard of care, and the abnormalities were evaluated based on a scoring system that had been previously validated among ECMO patients. Of the 25 patients, 8 (32%) had normal neuroimaging, 7 (28%) had mild to moderate neuroimaging abnormalities, and the other 10 (40%) had severe neuroimaging abnormalities. The degrees of cerebral autoregulation impairment quantified based on WTC showed significant correlations with the neuroimaging scores ([Formula: see text]; [Formula: see text]). Evidence that cerebral autoregulation impairment during ECMO was related to the patients' neurological outcomes was provided.

An International Survey on Ventilator Practices Among Extracorporeal Membrane Oxygenation Centers.

Although the optimal ventilation strategy is unknown for patients placed on extracorporeal support, there are increasing reports of extubation being used. Our objective was to describe the change in ventilation strategies and use of tracheostomy and bronchoscopy practices among extracorporeal membrane oxygenation (ECMO) centers across the world. A descriptive, cross-sectional 22 item survey of neonatal, pediatric, and adult ECMO centers was used to evaluate ventilator strategies, extubation, bronchoscopy, and tracheostomy practices. Extubation practices are increasing among all types of ECMO centers, representing 27% of all patients in pediatric centers, 41% of all patients in mixed centers, and 52% of all patients in adult centers. The most common mode of ventilation during ECMO is pressure control. There is a trend toward increased use of bilevel ventilation particularly for lung recruitment. Additionally, there is a trend toward increase in performance of bronchoscopy (pediatrics: 69%, mixed centers: 81%, adults: 76%) and tracheostomy. Among the centers performing tracheostomies, 45% reported the percutaneous method (pediatric: 31%, mixed: 46%, adult: 57%), 19% reported the open method (pediatric: 9%, mixed: 27%, adult: 24%), and 10% reported using both types of tracheostomies (pediatric: 2%, mixed: 8%, adult: 16%). Our study shows that ECMO centers are extubating their patients, performing tracheostomies and bronchoscopies on their patients more than in the previous years. There remains significant variation in ECMO ventilator strategies and management internationally. Future studies are needed to correlate these changes in practices to outcome benefits.

Perinatal chronic hypoxia induces cortical inflammation, hypomyelination, and peripheral myelin-specific T cell autoreactivity.

pCH is an important risk factor for brain injury and long-term morbidity in children, occurring during the developmental stages of neurogenesis, neuronal migration, and myelination. We show that a rodent model of pCH results in an early decrease in mature myelin. Although pCH does increase progenitor oligodendrocytes in the developing brain, BrdU labeling revealed a loss in dividing progenitor oligodendrocytes, indicating a defect in mature cell replacement and myelinogenesis. Mice continued to exhibited hypomyelination, concomitant with long-term impairment of motor function, weeks after cessation of pCH. The implication of a novel neuroimmunologic interplay, pCH also induced a significant egress of infiltrating CD4 T cells into the developing brain. This pCH-mediated neuroinflammation included oligodendrocyte-directed autoimmunity, with an increase in peripheral myelin-specific CD4 T cells. Thus, both the loss of available, mature, myelin-producing glial cells and an active increase in autoreactive, myelin-specific CD4 T cell infiltration into pCH brains may contribute to early pCH-induced hypomyelination in the developing CNS. The elucidation of potential mechanisms of hypoxia-driven autoimmunity will expand our understanding of the neuroimmune axis during perinatal CNS disease states that may contribute to long-term functional disability.