Brainstem disconnection: two additional patients and expansion of the phenotype.

Brainstem disconnection (BD) is a rare posterior fossa abnormality defined by the nearly complete absence of a brainstem segment with the rostral and caudal brainstem portions connected only by a thin cord of tissue. The outcome is poor and the majority of children die within the first 2 months of life without achieving developmental milestones. We report on the cases of two children with BD and a prolonged spontaneous survival. Neither patient required intubation or mechanical ventilation and each survived longer than 2 months (one child died at the age of 8 months, the other is alive at the age of 4.5 years). In addition, patient 1 is the only child with BD reported so far who achieved some developmental milestones. Although the long-term neurodevelopmental outcome of BD remains unfavorable, the expansion of the phenotypic spectrum may be important in terms of counseling.

Body and head position effects on regional lung ventilation in infants: An electrical impedance tomography study.

OBJECTIVE: To determine the effects of body and head positions on the spatial distribution of ventilation in nonintubated spontaneously breathing and mechanically ventilated infants using electrical impedance tomography (EIT). DESIGN AND SETTING: Prospective study in a neonatal intensive care unit. PATIENTS: Ten spontaneously breathing (gestational age 38 weeks, postnatal age 13 days) and ten mechanically ventilated infants (gestational age 35 weeks, postnatal age 58 days). INTERVENTIONS: Supine and prone postures with different head positions (midline and rotated to the left and right side). MEASUREMENTS AND RESULTS: The distribution of ventilation in the chest cross-section was repeatedly determined from EIT data in each body/head position studied. During spontaneous breathing the tidal volumes in the left lung region were reduced in the supine posture with the head turned to the left as well as in the prone posture with the head rotated to either side when compared with the supine posture with the head in the midline position. During mechanical ventilation the tidal volumes in the left lung region were unaffected by the body and head position except for the prone posture combined with the leftward head rotation which reduced them. In both types of ventilation the tidal volumes in the right lung region were unaffected by the change in body/head position. CONCLUSION: The results indicate that the spatial distribution of ventilation is influenced by the body and head position in spontaneously breathing infants. Prone posture with the leftward head rotation has the most prominent effect which is detectable even during mechanical ventilation.

Humidification of respired gases in neonates and infants.

Which temperature and humidity is optimal and can be recommended to the clinician? Some authors advocate the delivery of gas at body temperature and 100% relative humidity, which is equivalent to a water content of 44 mg/L [5,88,89]. They argue that energy neutrality is the best indicator of optimum humidity and that the intubated airway cannot be equated with the natural airway. Water loss as well as temperature and humidity gradients along the airway are necessary for mucociliary clearance and maintenance of the liquid layer of the airway epithelium, however [3]. Theoretical considerations and long-lasting experience in clinical practice support a setting that mirrors physiologic conditions even in the intubated airway. Thus, saturated gas at a temperature of 330 degrees to 35 degrees C should be delivered to the airway threshold of ventilated neonates and infants. Heated humidifiers and some HMEs can comply with these conditions. With active humidification (primarily the condensation of water) over humidification or possible malfunctions must be kept in mind. The neonatologist must consider increase in deadspace, water-retention capability, leak around the tracheal tube, and the slight increase in airway resistance when using HMEs. HMEs should not be used during weaning from ventilatory support in babies who have a body weight less than 2500 g.

Distribution of lung ventilation in spontaneously breathing neonates lying in different body positions.

OBJECTIVE: The aim of our study was to determine the effect of the irregular spontaneous breathing pattern and posture on the spatial distribution of ventilation in neonates free from respiratory disease by the non-invasive imaging method of electrical impedance tomography (EIT). Scanning of spontaneously breathing neonates is the prerequisite for later routine application of EIT in babies with lung pathology undergoing ventilator therapy. DESIGN: Prospective study. SETTING: Neonatal intensive care unit at a university hospital. PATIENTS: Twelve pre-term and term neonates (mean age: 23 days; mean body weight: 2,465 g; mean gestational age: 34 weeks; mean birth weight: 2,040 g). INTERVENTIONS: Change in body position in the sequence: supine, right lateral, prone, supine. MEASUREMENTS AND RESULTS: EIT measurements were performed using the Göttingen GoeMF I system. EIT scans of regional lung ventilation showing the distribution of respired air in the chest cross-section were generated during phases of rapid tidal breathing and deep breaths. During tidal breathing, 54.5+/-8.3%, 55.2+/-10.5%, 59.9+/-8.4% and 54.2+/-8.5% of inspired air (mean values +/- SD) were directed into the right lung in the supine, right lateral, prone and repeated supine postures respectively. During deep inspirations, the right lung ventilation accounted for 52.6+/-7.9%, 68.5+/-8.5%, 55.4+/-8.2% and 50.5+/-6.6% of total ventilation respectively. CONCLUSION: The study identified the significant effect of breathing pattern and posture on the spatial distribution of lung ventilation in spontaneously breathing neonates. The results demonstrate that changes in regional ventilation can easily be determined by EIT and bode well for the future use of this method in paediatric intensive care.

Gene expression of the Na-Ca2+ exchanger, SERCA2a and calsequestrin after myocardial ischemia in the neonatal rabbit heart.

BACKGROUND: Neonatal hearts are less susceptible to developing myocardial dysfunction after hypoxia and/or ischemia than adult hearts. Differences in intracellular calcium homeostasis may be responsible for reduced calcium overload of the immature myocardium leading to the observed protection against ischemia. OBJECTIVE: To assess differences in baseline and post-ischemic gene expression of calcium handling proteins after ischemia in neonatal and adult rabbit hearts. METHODS: We used isolated antegrade perfused rabbit hearts (age 2 days, 28 days, n = 32), which were exposed to ischemia and hypothermia simulating myocardial stunning comparable to neonatal asphyxia. Gene and protein expression of the sodium-calcium exchanger (NCX), the sarco-endoplasmatic reticulum Ca2+-ATPase 2a (SERCA) and calsequestrin (CSQ) were measured using quantitative real-time PCR and Western blotting. RESULTS: After ischemia and reperfusion in neonatal and adult hearts, a significant decrease in myocardial performance was recorded. At the mRNA level, significant differences in the baseline expression of NCX, SERCA and CSQ between neonatal and adult hearts were observed. In neonatal post-ischemic hearts, NCX and CSQ expression were significantly higher at the mRNA level than in controls. In contrast, SERCA expression remained unchanged in neonatal hearts and decreased in adult hearts compared to the non-ischemic controls. CONCLUSION: These findings suggest that changes in gene expression of calcium handling proteins may be involved in the different susceptibility of neonatal compared to adult hearts to developing myocardial dysfunction after ischemia.

Prenatal DNA diagnosis of Noonan syndrome in a fetus with massive hygroma colli, pleural effusion and ascites.

Prenatal molecular genetic diagnosis for Noonan syndrome I is reported. Noonan syndrome was suspected because of large cystic hygroma colli, massive pleural effusion and ascites at 23 weeks of gestation and normal karyotype (46,XX). DNA was prepared from amnion cells and screened for mutations in the PTPN11 gene. In exon 8, a missense mutation (S285F) was found. Delivery was induced at 33 weeks of gestation because of silent cardiotocography (CTG). Despite immediate drainage of the hydrothorax, mechanical ventilation was insufficient and the child died 9 h after birth due to severe pulmonary hypoplasia. Pleural punctate was enriched for small lymphocytes and thus was characterized as chylus. Prenatal ultrasound findings in Noonan syndrome usually are unspecific and rarely lead to a diagnosis. However, with the combination of cystic hygroma, pleural effusion, ascites and normal karyotype Noonan syndrome should be considered and DNA testing for PTPN11 mutations may be appropriate. Malformations of lymphatic vessels and/or chylothorax in Noonan syndrome seem to be more frequent than usually anticipated.

Effects of different inotropic interventions on myocardial function in the developing rabbit heart.

The development of the mammalian heart is characterized by substantial changes in myocardial performance. We studied the ontogeny of myocardial function with and without various inotropic interventions in the developing isolated, antegrade-perfused rabbit heart (2d, 8d, 14d, 28d, n = 96). Myocardial function was related to the protein expression of the sarcolemmal Na(+)-Ca2+ exchanger and to the sarcoplasmic Ca(2+)-ATPase. In neonatal hearts an age-dependent increase in maximal developed pressure velocity (dP/dtmax) by 45% and peak negative pressure velocity (dP/ dtmin) by 75% within days 2 to 8 were observed. In response to inotropic intervention with isoproterenol, ouabain, calcium and the Na(+)-channel modulator BDF 9148, dP/dtmax and dP/dtmin increased in a concentration dependent manner. Significant differences between neonatal, juvenile and adult hearts could be demonstrated in a repeated measurement ANOVA model on the concentration-response curves for BDF 9148 (dP/dtmax and dP/dtmin), ouabain (dP/dtmin) and calcium (dP/dtmin), but not for isoproterenol. At the maximum isoproterenol concentration of 1 micromol/l, the increase in dP/dtmax and dP/dtmin was significantly higher in adult compared to neonatal hearts (t-test, p < 0.01). The significant decline of the Na(+)-Ca2+ exchanger protein expression from neonatal (1822 +/- 171) to adult hearts (411 +/- 96 S.E.M. [units per 20 microg protein], p < 0.01) was related to an increase in myocardial function (dP/dtmax r = 0.63, p < 0.01, dP/dtmin r = 0.62, p < 0.01). Contractility, relaxation and the observed positive inotropic effects were in general significantly lower in neonatal compared to adult hearts. In the individual heart an increase in contractility and relaxation was related to a decrease in Na(+)-Ca2+ exchanger expression.

Assessment of cardiac output, intravascular volume status, and extravascular lung water by transpulmonary indicator dilution in critically ill neonates and infants.

OBJECTIVE: To assess cardiac output, intrathoracic blood volume, global end-diastolic volume, and extravascular lung water in critically ill neonates and small infants using transpulmonary indicator dilution. DESIGN: Prospective, observational, clinical study. SETTING: Pediatric intensive care unit in a university hospital. PARTICIPANTS: Critically ill neonates and small infants suffering from severe heart failure, respiratory failure, or sepsis (n = 10). INTERVENTIONS: A total of 194 transpulmonary indicator dilution measurements were done. Global end-diastolic volume, intrathoracic blood volume, and stroke volume were measured and compared with standard hemodynamic parameters during the clinical course and before and after volume loading (16 +/- 3.7 mL/kg of 10% albumin solution) in 8 of 10 patients. MEASUREMENTS AND MAIN RESULTS: A positive correlation was found for stroke volume index versus global end-diastolic volume (r = 0.76, p < 0.001) and intrathoracic blood volume (r = 0.56, p < 0.001). In contrast, no correlation was observed for stroke volume index versus central venous pressure. Volume loading resulted in significant increases in stroke volume index (p < 0.01), global end-diastolic volume (p < 0.01), and intrathoracic blood volume (p < 0.01); whereas central venous pressure, heart rate, mean arterial pressure, and extravascular lung water remained unchanged. CONCLUSION: Transpulmonary indicator dilution enables measurement of cardiac output and intravascular volume status in critically ill neonates and infants at the bedside. The effects of volume loading on cardiac preload and effective change in stroke volume can be monitored by this technique, whereas central venous pressure was not indicative of changes in intravascular volume status.

Na(+)-channel modulation, a new principle of inotropic intervention: effects on hemodynamic and myocardial energetics in the immature rabbit heart.

Na+-channel modulators exert their positive inotropic action without affecting the adenylate-cyclase pathway by an increase in the open probability of the sarcolemmal Na+ channels. Although inotropic effects in neonatal hearts are less pronounced compared with adult hearts, the Na+-channel modulator BDF 9148 increases contractility and relaxation velocity in immature myocardium. Effects on hemodynamics and myocardial energetics are not known. Therefore, we studied the Na+-channel modulator BDF 9148 in isolated antegrade perfused rabbit hearts of different ages (2-28 d) and compared the effects with isoproterenol, enoximone, and ouabain. ANOVA showed significant effects in the concentration response curves for heart rate, stroke volume, cardiac output, and oxygen consumption but not for myocardial efficiency (p = 0.06). Age-dependent differences were observed for heart rate and stroke volume. Administration of BDF 9148 resulted in a maximal increase in stroke volume and cardiac output up to 25% in neonatal and 40% to 60% in adult preparations. Heart rate decreased by 15% in adult hearts only. Myocardial oxygen consumption was increased in a concentration-dependent manner between 25% in neonatal and 50% in adult hearts. Myocardial efficiency was increased by 35% in adult and by 10% in neonatal preparations. Although positive hemodynamic and energetic effects were less pronounced in immature compared with adult hearts, neonatal hearts also profited from the administration of the Na+-channel modulator BDF 9148. Further studies are necessary to clarify the risk of arrhythmia during application of Na+-channel modulators such as BDF 9148.