Characteristics, outcomes, and 30-day readmissions following pediatric extracorporeal membrane oxygenation in the United States: A Nationwide Readmissions Database study.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) is an increasingly used mode of critical care support for pediatric patients refractory to conventional therapy. We evaluated the characteristics, outcomes, and readmissions rates for pediatric ECMO in the United States. METHODS: Data was extracted from the Nationwide Readmissions Database, a database designed to support national readmissions analyses, for patients aged 1-18 years undergoing ECMO between 2012-2018. Baseline demographics, comorbidities, and characteristics were identified using International Classification of Diseases codes. RESULTS: Out of 897,117 index pediatric hospitalizations, 3706 patients underwent ECMO [median age 9 years (IQR 2,15); 51.6% males]. 2246 (60.6%) patients survived to hospital discharge, with a 30-day readmissions rate of 17% among survivors. Cardiac conditions associated with ECMO were congenital heart disease (25.3%), cardiogenic shock (23.6%), and congestive heart failure (16.2%). The common respiratory associations were sepsis (36.2%), pneumonia (35.6%), and asthma (15.4%). Patients who survived were more likely to have diagnoses of asthma, bronchiolitis, myocarditis, pneumonia, and sepsis. Acute kidney injury (51.5%), disseminated intravascular coagulation (22.5%), and surgical site bleeding (12.7%) were the commonly associated complications. The trend for yearly survival rates was not statistically significant (linear p-trend = 0.38). CONCLUSIONS: Pediatric ECMO continues to be associated with notable mortality and complication rates. We did not observe a meaningful trend for the yearly survival rates over the study period, and over one-sixth of survivors were readmitted within 30-days. More research is needed to identify patients at high risk of mortality and readmissions, to help target resources more efficiently and improve survival.

Hyaluronidase and Hyaluronan Oligosaccharides Promote Neurological Recovery after Intraventricular Hemorrhage.

Intraventricular hemorrhage (IVH) in premature infants results in inflammation, arrested oligodendrocyte progenitor cell (OPC) maturation, and reduced myelination of the white matter. Hyaluronan (HA) inhibits OPC maturation and complexes with the heavy chain (HC) of glycoprotein inter-α-inhibitor to form pathological HA (HC-HA complex), which exacerbates inflammation. Therefore, we hypothesized that IVH would result in accumulation of HA, and that either degradation of HA by hyaluronidase treatment or elimination of HCs from pathological HA by HA oligosaccharide administration would restore OPC maturation, myelination, and neurological function in survivors with IVH. To test these hypotheses, we used the preterm rabbit model of glycerol-induced IVH and analyzed autopsy samples from premature infants. We found that total HA levels were comparable in both preterm rabbit pups and human infants with and without IVH, but HA receptors--CD44, TLR2, TLR4--were elevated in the forebrain of both humans and rabbits with IVH. Hyaluronidase treatment of rabbits with IVH reduced CD44 and TLR4 expression, proinflammatory cytokine levels, and microglia infiltration. It also promoted OPC maturation, myelination, and neurological recovery. HC-HA and tumor necrosis factor-stimulated gene-6 were elevated in newborns with IVH; and depletion of HC-HA levels by HA oligosaccharide treatment reduced inflammation and enhanced myelination and neurological recovery in rabbits with IVH. Hence, hyaluronidase or HA oligosaccharide treatment represses inflammation, promotes OPC maturation, and restores myelination and neurological function in rabbits with IVH. These therapeutic strategies might improve the neurological outcome of premature infants with IVH. Significance statement: Approximately 12,000 premature infants develop IVH every year in the United States, and a large number of survivors with IVH develop cerebral palsy and cognitive deficits. The onset of IVH induces inflammation of the periventricular white matter, which results in arrested maturation of OPCs and myelination failure. HA is a major component of the extracellular matrix of the brain, which regulates inflammation through CD44 and TLR2/4 receptors. Here, we show two mechanism-based strategies that effectively enhanced myelination and neurological recovery in preterm rabbit model of IVH. First, degrading HA by hyaluronidase treatment reduced CD44 and TLR4 expression, proinflammatory cytokines, and microglial infiltration, as well as promoted oligodendrocyte maturation and myelination. Second, intraventricular injection of HA oligosaccharide reduced inflammation and enhanced myelination, conceivably by depleting HC-HA levels.

Treatment with thyroxine restores myelination and clinical recovery after intraventricular hemorrhage.

Intraventricular hemorrhage (IVH) remains a major cause of white matter injury in preterm infants with no viable therapeutic strategy to restore myelination. Maturation of oligodendrocytes and myelination is influenced by thyroid hormone (TH) signaling, which is mediated by TH receptor α (TRα) and TRß. In the brain, cellular levels of TH are regulated by deiodinases, with deiodinase-2 mediating TH activation and deiodinase-3 TH inactivation. Therefore, we hypothesized that IVH would decrease TH signaling via changes in the expression of deiodinases and/or TRs, and normalization of TH signaling would enhance maturation of oligodendrocytes and myelination in preterm infants with IVH. These hypotheses were tested using both autopsy materials from human preterm infants and a rabbit model of IVH. We found that deiodinase-2 levels were reduced, whereas deiodinase-3 levels were increased in brain samples of both humans and rabbits with IVH compared with controls without IVH. TRα expression was also increased in human infants with IVH. Importantly, treatment with TH accelerated the proliferation and maturation of oligodendrocytes, increased transcription of Olig2 and Sox10 genes, augmented myelination, and restored neurological function in pups with IVH. Consistent with these findings, the density of myelinating oligodendrocytes was almost doubled in TH-treated human preterm infants compared with controls. Thus, in infants with IVH the combined elevation in deiodinase-3 and reduction in deiodinase-2 decreases TH signaling that can be worsened by an increase in unliganded TRα. Given that TH promotes neurological recovery in IVH, TH treatment might improve the neurodevelopmental outcome of preterm infants with IVH.

How we do it: acute management of subarachnoid hemorrhage.

OBJECTIVES: Acute subarachnoid hemorrhage (SAH) is a neurological emergency with significant potential for long-term morbidity and mortality. We review our management of acute SAH and some of the evidence base supporting our practices. METHODS: We reviewed our standardized and multi-disciplinary approach to the management of SAH. RESULTS: Management of SAH treatment can be divided into acute, aneurysmal, waiting, and post-waiting phases. Acute issues upon presentation include hemodynamic and respiratory stability, prevention of rebleeding, and treatment of hydrocephalus. The aneurysm must then be secured through endovascular or microsurgical methods. Observation for signs and symptoms of vasospasm must be closely undertaken. Prevention of subsequent medical complications must also be undertaken. Weaning from cerebrospinal fluid diversion and possible shunting is the final step. DISCUSSION: Standardized multi-modality management of rebleeding, hydrocephalus, aneurysmal obliteration, vasospasm, cerebral salt wasting, and other medical complications during these phases, is critical.