Care of the Neonate on Nasal Continuous Positive Airway Pressure: A Bedside Guide.

Respiratory distress continues to be a major cause of neonatal morbidity. Current neonatal practice recommends the use of nasal continuous positive airway pressure (nCPAP) in the immediate resuscitation and continued support of neonates of all gestations with clinical manifestations of respiratory distress. Despite the many short- and long-term benefits of nCPAP, many neonatal care units have met resistance in its routine use. Although there have been numerous recent publications investigating the use and outcomes of various modes of nCPAP delivery, surfactant administration, mechanical ventilation, and other forms of noninvasive respiratory support (high-flow nasal cannula, nasal intermittent positive pressure ventilation), there has been a relative lack of publications addressing the practical bedside care of infants managed on nCPAP. Effective use of nCPAP requires a coordinated interprofessional team approach, ongoing assessment of the neonate, troubleshooting the nCPAP circuit, and parent education.

Results of a Feeding Protocol in Patients Undergoing the Hybrid Procedure.

Neonates with single-ventricle physiology are at increased risk of developing gastrointestinal morbidities. Feeding protocols in this patient population have been shown to decrease feeding complications after the Norwood procedure, but no data exist to determine the effectiveness of a feeding protocol in patients undergoing the hybrid procedure. Goal of this study was to examine the impact of a standardized feeding protocol on the incidence of overall postoperative gastrointestinal morbidity after the hybrid procedure. Retrospective chart review was performed on neonates undergoing the hybrid procedure. Neonates were divided into two groups, pre-feeding protocol (pre-FP), which encompassed the years 2002-2008, and post-feeding protocol (post-FP), which encompassed the years 2011-2014. Preoperative, operative, and postoperative data were collected. T test or Fisher's exact test was used for analysis. p < 0.05 was considered significant. Seventy-three neonates were in the pre-FP and 52 neonates were in the post-FP. There were no significant differences between the pre-FP and the post-FP in cardiac diagnosis (62 HLHS, 11 other vs. 39 HLHS, 13 other, respectively). Pre-FP underwent hybrid procedure later than the post-FP (9.1 ± 5.8 vs. 5.7 ± 3.4 days, respectively, p < 0.01) and achieved full enteral feeds earlier than the post-FP (3.2 + 2.9 vs. 7.8 + 3.9 days, respectively, p < 0.01). The incidence of necrotizing enterocolitis was higher in the pre-FP versus post-FP [11.0 % (8/65) vs. 5.8 % (3/49), respectively, p = 0.36]. Though not significant, the incidence of necrotizing enterocolitis decreased by almost 50 % after initiating a feeding protocol in patients undergoing the hybrid procedure. This is consistent with previous studies showing beneficial results of a feeding protocol in this complex patient population.

Diastolic flow parameters are not sensitive in predicting necrotizing enterocolitis in patients undergoing hybrid procedure.

BACKGROUND: Necrotizing enterocolitis (NEC) is a significant cause of morbidity and mortality in neonates with complex single-ventricle anatomy undergoing stage I palliation. Hybrid approach is another option for initial single-ventricle palliation. The goal of this study was to determine if there were differences in echocardiographic indices between patients undergoing the hybrid procedure who developed NEC vs. those that did not develop NEC. METHODS: Retrospective chart review was performed on patients who underwent the hybrid procedure. Patients were included if an echocardiogram with adequate Doppler tracings through the patent ductus arteriosus stent was available. Echocardiographic indices measured included antegrade velocity-time integral (VTI), retrograde VTI, effective VTI, VTI regurgitant fraction, VTI retrograde/VTI antegrade ratio, calculated cardiac output, peak antegrade velocity through the ductal stent, retrograde/antegrade time ratio, and percent regurgitant time. Indices were compared in patients who developed NEC (NEC Group) and those who did not develop NEC (No NEC Group). NEC was defined as a Bell Stage ≥2. RESULTS: Sixty-nine patients met inclusion criteria. Eight of the 69 patients developed NEC. There was no significant difference between the NEC and No NEC Group for antegrade VTI (10.4 ± 3.2 cm vs. 12.7 ± 4.4 cm), retrograde VTI (5.3 ± 1.5 cm vs. 6.1 ± 2.2 cm), effective VTI (5.1 ± 2.9 cm vs. 6.6 ± 3.3 cm), VTI regurgitant fraction (53.6 ± 14.7% vs. 49.7 ± 13.6%), and VTI retrograde/VTI antegrade ratio (0.54 ± 0.15 vs.0.50 ± 0.14). Cardiac output (4.2 ± 1.4 L/min/m(2) vs. 4.8 ± 1.8 L/min/m(2) ) and peak velocity (117.5 ± 28.9 cm/s and 142.4 ± 42.6 cm/s) were also not different between the NEC and No NEC Groups. Furthermore, retrograde/antegrade time ratios (1.6 ± 0.2 vs. 1.7 ± 0.3) and percent retrograde time (60.6 ± 3.0% vs. 62.0 ± 4.0%) were not different between the NEC and No NEC Groups. CONCLUSION: Echocardiographic indices were not sensitive in determining the development of NEC in patients undergoing the hybrid procedure. Larger studies with more sensitive imaging techniques are required to help risk stratify NEC in this complex patient population.

MAPK signaling drives inflammation in LPS-stimulated cardiomyocytes: the route of crosstalk to G-protein-coupled receptors.

Profound cardiovascular dysfunction is an important cause of mortality from septic shock. The molecular underpinnings of cardiac dysfunction during the inflammatory surge of early sepsis are not fully understood. MAPKs are important signal transducers mediating inflammation whereas G-protein signaling pathways modulate the cardiac response to stress. Using H9c2 cardiomyocytes, we investigated the interaction of MAPK and G-protein signaling in a sepsis model to test the hypothesis that the cardiomyocyte inflammatory response is controlled by MAPKs via G-protein-mediated events. We found that LPS stimulated proinflammatory cytokine production was markedly exacerbated by siRNA knockdown of the MAPK negative regulator Mkp-1. Cytokine production was blunted when cells were treated with p38 inhibitor. Two important cellular signaling molecules typically regulated by G-protein-coupled receptors, cAMP and PKC activity, were also stimulated by LPS and inflammatory cytokines TNF-α and IL-6, through a process regulated by Mkp-1 and p38. Interestingly, neutralizing antibodies against Gα(s) and Gα(q) blocked the increase in cellular cAMP and PKC activation, respectively, in response to inflammatory stimuli, indicating a critical role of G-protein coupled receptors in this process. LPS stimulation increased COX-2 in H9c2 cells, which also express prostaglandin receptors. Blockade of G-protein-coupled EP4 prostaglandin receptor by AH 23848 prevented LPS-induced cAMP increase. These data implicate MAPKs and G-proteins in the cardiomyocyte inflammatory response to LPS as well as crosstalk via COX-2-generated PGE(2). These data add to our understanding of the pathogenesis of septic shock and have the potential to guide the selection of future therapeutics.

Necrotizing enterocolitis in neonates undergoing the hybrid approach to complex congenital heart disease.

OBJECTIVE: To investigate the prevalence of necrotizing enterocolitis (NEC) in neonates undergoing the Stage I hybrid procedure for palliation of complex congenital heart disease (CHD). Neonates undergoing the Norwood surgery for hypoplastic left-heart syndrome have the highest risk for NEC of all CHD patients. The hybrid procedure is another palliative option for hypoplastic left-heart syndrome, but NEC in neonates undergoing this procedure has not been reported. DESIGN: Retrospective chart review of 73 neonates who underwent the hybrid procedure for palliation of complex CHD. Demographic, perinatal, perioperative, clinical, and procedural data were collected. NEC was defined as modified Bell's Stage II and above. SETTING: The cardiothoracic and neonatal intensive care units in a large free-standing children's hospital. PATIENTS: All neonates who underwent the hybrid Stage I procedure for the palliation of complex CHD from April 2002 through April 2008. MEASUREMENTS AND MAIN RESULTS: Seventy-three neonates were reviewed and 11.0% (eight of 73) developed NEC. Of the patients with NEC, 37.5% (three of eight) died and two patients required abdominal surgery. Earlier gestational age (< 37 wks), lower maximum dose of prostaglandin infusion, and unexpected readmission to the intensive care unit were statistically associated with NEC (p = .009, 0.02, and 0.04, respectively). No other demographic, perinatal, perioperative, clinical, or procedural variables were associated with the development of NEC in this patient population, including enteral feeding regimens, umbilical artery catheters, inotrope use, and average oxygen saturation and diastolic blood pressure. CONCLUSIONS: The prevalence of NEC in patients undergoing the hybrid procedure is comparable to that reported for neonates undergoing the Norwood procedure. Earlier gestational age is a significant risk factor for NEC in patients who undergo the hybrid Stage I procedure. Multidisciplinary approaches to better understand abdominal complications and to develop feeding regimens in neonates undergoing the hybrid approach to complex CHD are needed to improve outcomes and decrease morbidities.

Necrotizing enterocolitis in neonates with congenital heart disease.

Both necrotizing enterocolitis (NEC) and congenital heart disease (CHD) are causes of significant morbidity and mortality in the neonatal population. While two distinct disease processes, NEC and CHD are inter-related as the incidence of NEC is greater in neonates with CHD than the normal newborn population. It is likely that circulatory perturbations, especially those seen in infants with left ventricular outflow tract lesions and single ventricle physiology, the stress of cardiac surgery and cardiopulmonary bypass, and the underlying baseline elevation of circulating endotoxin and proinflammatory cytokines all play a role in the pathogenesis of NEC in this uniquely susceptible population. The neurodevelopmental impairment in infants requiring surgery for NEC and in infants with complex congenital heart disease is alarming and requires further investigation. As medical and surgical advances allow for the palliation and correction of complex lesions at an earlier gestational age and lower birth weight, the already high risk of NEC in this population is likely to increase. This will require more aggressive study of the etiology of NEC in patients with CHD and the development of preventative therapies in order to decrease the impressive morbidity and mortality associated with the combination of these disease processes. In this article, we review the pathogenesis of NEC and CHD including associated mortality and morbidities and discuss possible mechanisms linking these two disease states.

Bench-to-bedside review: Developmental influences on the mechanisms, treatment and outcomes of cardiovascular dysfunction in neonatal versus adult sepsis.

Sepsis is a significant cause of morbidity and mortality in neonates and adults, and the mortality rate doubles in patients who develop cardiovascular dysfunction and septic shock. Sepsis is especially devastating in the neonatal population, as it is one of the leading causes of death for hospitalized infants. In the neonate, there are multiple developmental alterations in both the response to pathogens and the response to treatment that distinguish this age group from adults. Differences in innate immunity and cytokine response may predispose neonates to the harmful effects of pro-inflammatory cytokines and oxidative stress, leading to severe organ dysfunction and sequelae during infection and inflammation. Underlying differences in cardiovascular anatomy, function and response to treatment may further alter the neonate's response to pathogen exposure. Unlike adults, little is known about the cardiovascular response to sepsis in the neonate. In addition, recent research has demonstrated that the mechanisms, inflammatory response, response to treatment and outcome of neonatal sepsis vary not only from that of adults, but vary among neonates based on gestational age. The goal of the present article is to review key pathophysiologic aspects of sepsis-related cardiovascular dysfunction, with an emphasis on defining known differences between adult and neonatal populations. Investigations of these relationships may ultimately lead to 'neonate-specific' therapeutic strategies for this devastating and costly medical problem.