Objective To test for associations between abnormal respiratory ciliary motion (CM) and brain abnormalities in infants with congenital heart disease (CHD) Study design We recruited 35 infants with CHD preoperatively and performed nasal tissue biopsy to assess respiratory CM by videomicroscopy. Cranial ultrasound and brain magnetic resonance imaging were obtained pre- and/or post-operatively and systematically reviewed for brain abnormalities. Segmentation was used to quantitate cerebrospinal fluid and regional brain volumes. Perinatal and perioperative clinical variables were collected. Results A total of 10 (28.5%) patients with CHD had abnormal CM. Abnormal CM was not associated with brain injury, but was correlated with increased extra-axial CSF volume (p<0.001), delayed brain maturation (p<0.05), and a spectrum of subtle dysplasia including the hippocampus (p<0.0078) and olfactory bulb (p<0.034). Abnormal CM was associated with higher composite dysplasia score (p<0.001) and both were correlated with elevated pre-operative serum lactate (p <0.001). Conclusion Abnormal respiratory CM in infants with CHD is associated with a spectrum of brain dysplasia. These findings suggest that ciliary defects may play a role in brain dysplasia in patients with CHD and have the potential to prognosticate neurodevelopmental risks.

Chylothorax after cardiac surgery in children is associated with significant morbidity and mortality. A five-fold variation in chylothorax rates was observed across centres. Future investigations should identify centres most adept at preventing and managing chylothorax and disseminate best practices.

We provide comprehensive multicenter benchmark data regarding rates of HAIs within dedicated pediatric CICUs. We confirm that although rare, HAIs of all types are associated with significant resource utilization and mortality.

Aim Nasal cannulas are used to provide oxygen support for infants and have been considered as a means for delivering aerosols to the lungs. To measure mucociliary clearance in the lungs of infants with congenital heart defects, we delivered radiopharmaceutical aerosols via a nasal cannula. Here we report on the pulmonary and nasal deposition of these aerosols. Method A total of 18 infants (median age = 26 days; quartiles = 11‐74 days) performed clearance measurements soon before or after corrective cardiac surgery. The regional aerosol deposition was assessed using gamma camera imaging. Results Cannula flow rate significantly affected pulmonary dosing. Flow rates useful for oxygen support were associated with low pulmonary deposition (2 L/min; mean, 4.5% of deposited dose; range, 2%‐9%; n = 7) and high nasal deposition. Much lower cannula flow rates increased the pulmonary deposition (0.2 L/min; mean, 33.5% of deposited dose; range, 15%‐51%; n = 5; P = 0.005 vs 2 L/min). The ratio of nose/lung dosing was approximately 26:1 at 2 L/min and 2:1 at 0.2 L/min. Bench studies demonstrated cannula output rates of 10.2 ± 1.7% (2 L/min) and 3.3 ± 0.4% (0.2 L/min) of the loaded nebulizer dose during a 2‐minute delivery. Combining in vitro and in vivo results, we estimate that 0.46% of the loaded nebulizer dose reaches the lungs at 2 L/min vs 1.10% at 0.2 L/min during a 2‐minute delivery. Conclusion With the delivery system used here, pulmonary aerosol delivery via nasal cannula was very inefficient at the flow rates required to provide oxygen support. Even at low flows, nasal deposition was substantial and local toxicity must be considered.

Objective: Examine the relationship between perioperative renal regional oximetry (rSO2), urinary biomarkers, and acute kidney injury (AKI) in infants after congenital cardiac surgery with cardiopulmonary bypass. Design: Prospective, observational. Setting: Cardiac operating room and intensive care unit (CICU) Patients: Neonates and infants without history of kidney injury or anatomic renal abnormality. Interventions: None. Measurements and Main Results: Renal rSO2 was measured intraoperatively and for 48 hours postoperatively. Urinary levels of neutrophil gelatinase-associated lipocalin (NGAL) and tissue inhibitor of metalloproteinases 2 (TIMP-2) together with insulin-like growth factor-binding protein 7 (IGFBP7) were measured preoperatively, 2, 12, and 24 hours postoperatively. Patients were categorized as no AKI, Stage 1, or Stage 2–3 AKI using KDIGO criteria with 43/70 (61%) meeting criteria for any stage AKI. Stage 2–3 AKI patients had higher [TIMP-2]•[IGFBP7] at 2 hours (0.3 vs. 0.14 for Stage 1 AKI and 0.05 for no AKI, P=0.052) and 24 hours postop (1.71 vs. 0.27 for Stage 1 AKI and 0.19 for no AKI, P=0.027) and higher NGAL levels at 24 hours postop (10.3 vs. 3.4 for Stage 1 AKI and 6.2 for no AKI, P=0.019). Stage 2–3 AKI patients had lower mean CICU renal rSO2 (66% vs. 79% for Stage 1 AKI and 84% for no AKI, P=0.038). Regression analyses showed that [TIMP-2]•[IGFBP7] at 2 hours postop and nadir intraoperative renal rSO2 to be independent predictors of postoperative kidney damage as measured by urinary NGAL. Conclusions: We observed modest differences in perioperative renal rSO2 and urinary biomarker levels compared between AKI groups classified by creatinine-dependent KDIGO criteria, but there were significant correlations between renal rSO2, [TIMP-2]•[IGFBP7], and postoperative NGAL levels. Kidney injury after infant cardiac surgery may be undetectable by functional assessment (creatinine) alone and continuous monitoring of renal rSO2 may be more sensitive to important subclinical AKI.

ObjectiveThe critically ill, premature patients of neonatal intensive care units are susceptible to venous thrombosis, an adverse event associated with short- and long-term morbidity. Venous thrombosis is frequently treated with low molecular weight heparins (LMWH) such as enoxaparin, but optimal dosing of LMWH must balance the morbidity of venous thrombosis with the potential adverse affects of anticoagulation. The optimal dosing of enoxaparin for premature infants is unclear. The objective of this study was to describe enoxaparin therapy and follow-up in critically ill neonates diagnosed with venous thrombosis.Study DesignRetrospective medical record review in the neonatal intensive care unit (NICU) in a single tertiary care institution. Infants with venous thrombosis diagnosed in the NICU were identified using pre-existing quality improvement lists and medical records.ResultsTwenty-six infants with 30 venous thromboses were identified with a median gestational age of 31 weeks at birth. Eighteen (69%) infants received enoxaparin for venous thrombosis during their hospitalization, beginning with a median dose of 1.5 mg/kg every 12h. This dose was increased to a median 2.1 mg/kg every 12h to achieve target anti-factor Xa levels. The target dose was significantly higher in patients with a postmenstrual age less than 37 weeks. Enoxaparin treatment was documented after discharge in 12 patients, continuing for a median of 99 days. Four patients died during hospitalization and their deaths were not attributable to venous thrombosis or anticoagulation complication. Follow-up documentation between 6 and 24 months after venous thrombosis diagnosis revealed no major morbidity of venous thrombosis or enoxaparin therapy.ConclusionsOur data reinforces the relative safety and necessity of enoxaparin doses above 1.5 mg/kg per 12 hours in most neonates. This was particularly true for infants at lower postmenstrual age.

No abstract

Application of controlled release technology to the peritoneum would allow for sustained drug levels. However, some polymeric systems either create adhesions, or rapidly exit the peritoneum; neither result is desirable. Here we have produced particles based on sphyngomyelin, a phospholipid that occurs naturally in the peritoneum, along with hyaluronic acid and the polymethacrylate Eudragit E100 (to modulate drug release). Particles with a low proportion of E100 (5% (w/w); "high SPM") release albumin rapidly over 2 days, then more slowly; increasing the E100 to 20% (w/w; high "E100") slowed drug release markedly. When injected in the murine peritoneum, high SPM particles were disseminated as free particles, without forming collections. There was a mild inflammatory response but no formation of adhesions. High E100 particles formed collections in all animals, with an intense inflammatory response. Even so, there were very few adhesions. These results suggest that microparticulate formulations can be produced that have acceptable drug-releasing properties and are suitable for use in the peritoneum from the standpoint of biocompatibility.