Update on ventilation management in the Pediatric Intensive Care Unit.

Studies have shown that up to 63% of pediatric intensive care unit patients admitted with acute respiratory or cardiorespiratory illness require mechanical ventilation. Mechanical ventilator support can be divided into three phases: initiation, escalation, and resolution. Noninvasive ventilation is typical during the initiation phase in the management of acute pediatric respiratory failure. The major advancements in the use of noninvasive ventilation involve the emergence of high-flow nasal cannula and how widespread the use of high-flow nasal cannula has become in pediatric critical care practice. When high-flow nasal cannula fails, escalation to continuous positive airway pressure or bi-level positive airway pressure is the next step in respiratory care progression. Careful clinical assessment is necessary to avoid delayed escalation between forms of noninvasive support or escalation to intubation and invasive mechanical ventilation. Advancements in conventional mechanical ventilation are centered on optimizing ventilator settings and customizing monitoring with the overarching goal to reduce complications of mechanical ventilation, such as ventilator-induced lung injury. New mechanical ventilator strategies integrating esophageal pressure monitoring, volumetric capnography, and neurally adjusted ventilator assist help to optimize conventional ventilator support. Nonconventional modes of ventilation in the intensive care unit are high-frequency modes and airway pressure release ventilation. Extracorporeal pulmonary support via extracorporeal membrane oxygenation or paracorporeal lung assist devices provides rescue options when conventional and nonconventional methods fail. During resolution of a course of mechanical ventilator support, reliable weaning strategies and extubation readiness testing are lacking in pediatric critical care. Further, timing of tracheostomy, risk reduction in ventilator-induced lung injury, and decreased sedation requirements in pediatric patients requiring mechanical ventilation in the pediatric intensive care unit are areas of ongoing research.

Neurologic Injury in Neonates Undergoing Cardiac Surgery.

Neurodevelopmental outcomes after neonatal congenital heart surgery are significantly influenced by brain injury detectable by MRI imaging techniques. This brain injury can occur in the prenatal and postnatal periods even before cardiac surgery. Given the significant incidence of new MRI brain injury after cardiac surgery, much work is yet to be done on strategies to detect, prevent, and treat brain injury in the neonatal period in order to optimize longer-term neurodevelopmental outcomes.

Up-regulation of SFTPB expression and attenuation of acute lung injury by pulmonary epithelial cell-specific NAMPT knockdown.

Although a deficiency of surfactant protein B (SFTPB) has been associated with lung injury, SFTPB expression has not yet been linked with nicotinamide phosphoribosyltransferase (NAMPT), a potential biomarker of acute lung injury (ALI). The effects of Nampt in the pulmonary epithelial cell on both SFTPB expression and lung inflammation were investigated in a LPS-induced ALI mouse model. Pulmonary epithelial cell-specific knockdown of Nampt gene expression, achieved by the crossing of Nampt gene exon 2 floxed mice with mice expressing epithelial-specific transgene Cre or by the use of epithelial-specific expression of anti-Nampt antibody cDNA, significantly attenuated LPS-induced ALI. Knockdown of Nampt expression was accompanied by lower levels of bronchoalveolar lavage (BAL) neutrophil infiltrates, total protein and TNF-α levels, as well as lower lung injury scores. Notably, Nampt knockdown was also associated with significantly increased BAL SFTPB levels relative to the wild-type control mice. Down-regulation of NAMPT increased the expression of SFTPB and rescued TNF-α-induced inhibition of SFTPB, whereas overexpression of NAMPT inhibited SFTPB expression in both H441 and A549 cells. Inhibition of NAMPT up-regulated SFTPB expression by enhancing histone acetylation to increase its transcription. Additional data indicated that these effects were mainly mediated by NAMPT nonenzymatic function via the JNK pathway. This study shows that pulmonary epithelial cell-specific knockdown of NAMPT expression attenuated ALI, in part, via up-regulation of SFTPB expression. Thus, epithelial cell-specific knockdown of Nampt may be a potential new and viable therapeutic modality to ALI.-Bi, G., Wu, L., Huang, P., Islam, S., Heruth, D. P., Zhang, L. Q., Li, D.-Y., Sampath, V., Huang, W., Simon, B. A., Easley, R. B., Ye, S. Q. Up-regulation of SFTPB expression and attenuation of acute lung injury by pulmonary epithelial cell-specific NAMPT knockdown.

Static cerebrovascular pressure autoregulation remains intact during deep hypothermia.

BACKGROUND: Clinical studies measuring cerebral blood flow in infants during deep hypothermia have demonstrated diminished cerebrovascular pressure autoregulation. The coexistence of hypotension in these cohorts confounds the conclusion that deep hypothermia impairs cerebrovascular pressure autoregulation. AIM: We sought to compare the lower limit of autoregulation and the static rate of autoregulation between normothermic and hypothermic piglets. METHODS: Twenty anesthetized neonatal piglets (5-7 days old; 10 normothermic and 10 hypothermic to 20°C) had continuous measurements of cortical red cell flux using laser Doppler flowmetry, while hemorrhagic hypotension was induced without cardiopulmonary bypass. Lower limit of autoregulation was determined for each subject using piecewise regression and SRoR was determined above and below each lower limit of autoregulation as (%change cerebrovascular resistance/%change cerebral perfusion pressure). RESULTS: The estimated difference in lower limit of autoregulation was 1.4 mm Hg (lower in the hypothermic piglets; 95% C.I. -10 to 14 mm Hg; P=0.6). The median lower limit of autoregulation in the normothermic group was 39 mm Hg [IQR 38-51] vs 35 mm Hg [31-50] in the hypothermic group. Intact steady-state pressure autoregulation was defined as static rate of autoregulation >0.5 and was demonstrated in all normothermic subjects (static rate of autoregulation=0.72 [0.65-0.87]) and in 9/10 of the hypothermic subjects (static rate of autoregulation=0.65 [0.52-0.87]). This difference in static rate of autoregulation of 0.06 (95% C.I. -0.3 to 0.1) was not significant (P=0.4). CONCLUSION: Intact steady-state cerebrovascular pressure autoregulation is demonstrated in a swine model of profound hypothermia. Lower limit of autoregulation and static rate of autoregulation were similar in hypothermic and normothermic subjects.

A Novel Electrocardiogram Algorithm Utilizing ST-Segment Instability for Detection of Cardiopulmonary Arrest in Single Ventricle Physiology: A Retrospective Study.

OBJECTIVE: We evaluated ST-segment monitoring to detect clinical decompensation in infants with single ventricle anatomy. We proposed a signal processing algorithm for ST-segment instability and hypothesized that instability is associated with cardiopulmonary arrests. DESIGN: Retrospective, observational study. SETTING: Tertiary children's hospital 21-bed cardiovascular ICU and 36-bed step-down unit. PATIENTS: Twenty single ventricle infants who received stage 1 palliation surgery between January 2013 and January 2014. Twenty rapid response events resulting in cardiopulmonary arrests (arrest group) were recorded in 13 subjects, and nine subjects had no interstage cardiopulmonary arrest (control group). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Arrest data were collected over the 4-hour time window prior to cardiopulmonary arrest. Control data were collected from subjects with no interstage arrest using the 4-hour time window prior to cardiovascular ICU discharge. A paired subgroup analysis was performed comparing subject 4-hour windows prior to arrest (prearrest group) with 4-hour windows prior to discharge (postarrest group). Raw values of ST segments were compared between groups. A 3D ST-segment vector was created using three quasi-orthogonal leads (II, aVL, and V5). Magnitude and instability of this continuous vector were compared between groups. There was no significant difference in mean unprocessed ST-segment values in the arrest and control groups. Utilizing signal processing, there was an increase in the ST-vector magnitude (p = 0.02) and instability (p = 0.008) in the arrest group. In the paired subgroup analysis, there was an increase in the ST-vector magnitude (p = 0.05) and instability (p = 0.05) in the prearrest state compared with the postarrest state prior to discharge. CONCLUSIONS: In single ventricle patients, increased ST instability and magnitude were associated with rapid response events that required intervention for cardiopulmonary arrest, whereas conventional ST-segment monitoring did not differentiate an arrest from control state.

Alteration in the lower limit of autoregulation with elevations in cephalic venous pressure.

OBJECTIVES: Recent studies suggest that elevated intracranial pressure (ICP), created by hydrocephalus, can alter the lower limit of cerebrovascular autoregulation (LLA). Our objective in the present study was to determine if ICP elevation from cerebral venous outflow obstruction would result in comparable alterations in the LLA. METHODS: Anesthetized juvenile pigs were assigned to one of two groups: naïve ICP (n  =  15) or high ICP (>20 mmHg; n  =  20). To elevate ICP through venous obstruction, a modified 5F esophageal balloon catheter was inserted via the right external jugular vein into the superior vena cava (SVC) and inflated to maintain an ICP of >20 mmHg. To calculate the LLA, gradual hypotension was induced by continuous hemorrhage from a catheter in the femoral vein. The LLA was determined by monitoring cortical laser Doppler flux (LDF). RESULTS: The naïve and high ICP groups had LLAs of 45 mmHg (95% CI: 41-49 mmHg) and 71 mmHg (95% CI: 66-77 mmHg) respectively by LDF. The LLA was significantly different between the two groups and correlated significantly with ICP. DISCUSSION: Elevated ICP from cephalic venous engorgement leads to an increase in the LLA. These findings suggest that pathologic processes resulting in cephalic venous outflow obstruction and intracranial venous congestion can acutely elevate ICP and may place the brain at risk for impaired cerebrovascular autoregulation.