Tongue reduction in Beckwith-Wiedemann syndrome: outcome and treatment algorithm.

Beckwith-Wiedemann syndrome is a rare congenital overgrowth disorder with macroglossia being one of the cardinal symptoms. In pronounced cases, macroglossia can lead to airway obstruction, musculoskeletal alterations and functional deficits. Surgical tongue reduction is performed at varying ages and with different techniques. This study evaluated perioperative complications, as well as long-term aesthetic and functional outcomes, in a large cohort. A total of 68 patients, treated either surgically or conservatively, were included. Depending on the severity of macroglossia, patients were divided into three groups to determine the treatment algorithm. Complications after surgical tongue reduction were prolonged intubation and revision due to dehiscence or haematoma. In the long term, no patient suffered from impaired sense of taste or paresthesia, although the shape of the tongue was disproportional in 85%. With the present treatment algorithm, operative tongue reduction exerts a positive influence on skeletal, dentoalveolar and functional development with sufficient long-term outcome and high grade of satisfaction of the patients. Supportive therapy in an interdisciplinary centre is of fundamental importance for both surgical and conservative treatment.

Meta-analysis of inhaled nitric oxide in premature infants: an update.

INTRODUCTION: The role of inhaled nitric oxide (iNO) in the treatment of severe hypoxemic respiratory failure of term neonates has been firmly established in several randomized trials. In contrast, the use of iNO in premature newborns has remained controversial. We performed a meta-analysis of five published randomized controlled trials involving a total of 808 infants below 34 weeks of gestation. RESULTS: The rates of major intracranial hemorrhage (ICH) were similar in both groups (42 of 208 infants receiving iNO vs 52 of 185 controls, relative risk (RR) 0.72, 95 % confidence interval (CI) 0.50-1.02) as was the mortality rate (169 of 415 receiving iNO vs 155 of 393 controls, RR 1.03, 95 % CI 0.87-1.22). Of 415 infants receiving iNO, 188 infants were diagnosed as having chronic lung disease (CLD), compared to 215 of 393 control infants. The RR in favor of iNO was 0.83, 95 % CI 0.72-0.95, p = 0.0092. Treatment failure, defined as death or CLD was significantly reduced in the iNO group (iNO: 126 of 208 infants versus control: 139 of 185, RR in favor of iNO 0.81, 95 % CI 0.70-0.93, p = 0.0025). CONCLUSIONS: We conclude that the use of iNO may decrease the CLD and the combined endpoint CLD and mortality in preterm infants with hypoxemic respiratory failure. However, the most recent and by far largest study was terminated due to an increase in severe ICH. Therefore a cautious use of iNO in preterm infants at risk for ICH is mandatory. Further studies with appropriate neurodevelopmental follow-up need to elucidate if the reduction of CLD in very low birth weight infants is potentially associated with modifications in neurodevelopmental outcome.

Alveolar recruitment promotes homogeneous surfactant distribution in a piglet model of lung injury.

Uneven distribution of exogenous surfactant contributes to a poor clinical response in animal models of respiratory distress syndrome. Alveolar recruitment at the time of surfactant administration may lead to more homogeneous distribution within the lungs and result in a superior clinical response. To investigate the effects of three different volume recruitment maneuvers on gas exchange, lung function, and homogeneity of surfactant distribution, we studied 35 newborn piglets made surfactant deficient by repeated airway lavage with warm saline. Volume recruitment was achieved by either a temporal increase in tidal volume or an increase in end-expiratory pressure during surfactant administration, yielding an increase in dynamic compliance of the respiratory system of 77% in the first group and an increase in functional residual capacity of 108% in the second group. A third group of piglets (all n = 7) received a combination of both volume recruitment maneuvers, with increases in dynamic compliance of the respiratory system of 100% and in functional residual capacity of 192%. Those animals subjected to increased tidal volume showed an improved surfactant response in terms of oxygenation, ventilation, lung volumes, lung mechanics, and homogeneity of surfactant distribution. Increased end-expiratory volume augmented the surfactant effect only to some extent. The combination of both volume recruitment maneuvers, however, needed lung volumes beyond total lung capacity (approximately 56 mL/kg), thus probably inducing early sequelae of ventilator-induced lung injury. We conclude that volume recruitment by means of increased tidal volumes at the time of surfactant administration leads to a superior surfactant effect owing to more homogeneous surfactant distribution within a collapsed lung.

Response to inhaled nitric oxide in premature and term neonates.

Inhaled nitric oxide (iNO) has emerged as a promising therapeutic agent in the treatment of persistent pulmonary hypertension of the newborn. Several theories exist regarding causes of both response and nonresponse to iNO. Clinical trials differentiate disease entities (primary vs secondary persistent pulmonary hypertension associated with meconium aspiration syndrome, pneumonia or congenital diaphragmatic hernia) and their specific response rates. iNO combined with high-frequency ventilation appears to be superior to inhalation of nitric oxide (NO) during conventional ventilation. Little is known regarding the role of the degree of lung expansion and its modification -- no matter what mode of ventilation is applied. Gestational age plays an important role in relation to the potential adverse effects of NO. Of particular concern in the premature neonate is the effect of NO on bleeding time and the inhibition of platelet aggregation. Those potentially hazardous effects need to be carefully weighed against early intervention with iNO at a comparably low oxygenation index in order to prevent the vicious cycle of hypoxaemia and subsequent increased right-to-left shunting. Further studies are required to determine the optimal timing, mode of delivery and mode of ventilation used with iNO therapy in order to optimise the response of premature and term neonates.

Chest physiotherapy in mechanically ventilated children: a review.

OBJECTIVE: Many physicians, nurses, and respiratory care practitioners consider chest physiotherapy (CP) a standard therapy in mechanically ventilated children beyond the newborn period. CP includes percussion, vibration, postural drainage, assisted coughing, and suctioning via the endotracheal tube. DATA SOURCES: We searched the medical literature by using the key words "chest physiotherapy" and "chest physical therapy" (among others) by means of the MEDLINE and Current Contents databases. STUDY SELECTION: Because of the paucity of objective data, we examined all reports dealing with this topic, including studies on adult patients. For data extraction, not enough material existed to perform a meta-analysis. DATA SYNTHESIS: Despite its widespread use, almost no literature dealing with this treatment modality in pediatric patients exists. Studies with mechanically ventilated pediatric and adult patients have shown that CP is the most irritating routine intensive care procedure to patients. An increase in oxygen consumption often occurs when a patient receives CP accompanied by an elevation in heart rate, blood pressure, and intracranial pressure. CP leads to short-term decreases in oxygen, partial pressure in the blood, and major fluctuations in cardiac output. Changes in these vital signs and other variables may be even more pronounced in pediatric patients because the lung of a child is characterized by a higher closing capacity and the chest walls are characterized by a much higher compliance, thus predisposing the child to the development of atelectasis secondary to percussion and vibration. CONCLUSION: CP in mechanically ventilated children may not be considered a standard therapy. Controlled studies examining the impact of CP on the duration of mechanical ventilatory support, critical illness, and hospital stay are needed.

A new simple method of staining exogenous surfactant in experimental research.

Two commonly used techniques in experimental lung research have helped to determine which variables influence surfactant distribution within the lung: radioactive labelling of surfactant components and admixture of coloured microspheres to surfactant. However, neither technique allows the description of surfactant distribution at the alveolar level. The aim of this study was to establish a new technique using histology colourants for admixture to exogenous surfactant to make exogenous surfactant visible by light microscopy. In a step by step approach the authors evaluated the properties of a variety of green colourants when added to a natural porcine surfactant preparation for their ability to homogeneously mix with surfactant, to bind to surfactant, to adhere to a glass slide, to not be "overstained" by standard haematoxylin-eosin and Elastica van Giesson staining, to not influence in vitro surface tension properties of surfactant using a Wilhelmy balance, to not influence oxygenation and ventilation in a lung-lavage rat model and to preserve their colour and adherence to exogenous surfactant on lung specimens visualized by light microscopy. Only one of the tested green histology colourants (Green Dye) fulfilled all requirements and showed a brilliant green colour in a distribution pattern typical of surfactant at the alveolar level. It is concluded that the authors have established a new, simple and inexpensive method of staining exogenous surfactant for evaluation of its distribution by light microscopy at the alveolar level.

[Inhaled nitric oxide therapy in preterm infants]. / Inhalative Stickstoffmonoxidtherapie bei Frühgeborenen.

According to a number of recently published, randomized controlled trials, treatment of persistent pulmonary hypertension of the newborn (PPHN) by the use of inhaled nitric oxide (iNO) has emerged as an established procedure in neonatology. The situation in premature infants appears to be more complicated than in the term infant. Due to the fact that nitric oxide interferes with platelet aggregation, the risk of intraventricular hemorrhage or its aggravation during iNO therapy is being discussed in a controversial manner. Since most studies are aimed at endpoints like oxygenation parameters, the presently available studies report extremely variable incidences of intraventricular hemorrhages (IVH). Meanwhile two large studies could demonstrate that clinical application of iNO in preterm infants is not associated with an increased incidence of IVH. Further randomized controlled trials of iNO in preterm neonates are highly desirable in order to establish the future role of this therapy and its indications.

Inhaled nitric oxide in premature infants--a meta-analysis.

The role of inhaled nitric oxide (iNO) in the treatment of severe hypoxemic respiratory failure of term neonates has been firmly established in several randomized trials. In contrast, the use of iNO in premature newborns has remained controversial. As of 1999, there are data of three randomized controlled trials involving a total of 210 infants below 33 weeks of gestation. None of the trials was able to demonstrate a benefit of iNO with respect to mortality or chronic lung disease. We performed a meta-analysis of the three published trials. Of 111 infants receiving iNO, 44 deaths were observed, compared to 40 of 99 control infants (p = 0.91). The odds ratio in favor of iNO was 0.97 (95% confidence interval 0.54-1.75). There was also no significant difference for treatment failure, defined as death or chronic lung disease (iNO: 32 of 111 infants versus control: 34 of 99, p = 0.39, odds ratio 0.77, 95% confidence interval 0.41-1.45). The rates of intracranial hemorrhage were similar in both groups (35 of 111 infants receiving iNO vs 25 of 99 controls, p = 0.33, odds ratio 1.37, 95% confidence interval 0.69-2.74). We conclude that the use of inhaled nitric oxide may improve oxygenation but not survival in preterm infants with severe hypoxemic respiratory failure.

Timing of surfactant administration determines its physiologic response in a rabbit model of airway lavage.

Surfactant response depends on timing of surfactant administration in infants with respiratory distress syndrome (RDS). We performed lung function studies in an animal model to describe the underlying differences in response related to gas exchange, lung volume and lung mechanics comparing early and late surfactant administration protocols. Young New Zealand rabbits were made surfactant deficient by repeated airway lavage with warm saline until the a/A O(2) ratio decreased to

Comparison of noise levels caused by four different neonatal high-frequency ventilators.

OBJECTIVE: To test the hypothesis that neonatal high-frequency ventilators create different noise levels depending upon ventilator settings and device-specific properties. MATERIALS: Three neonatal ventilators with built-in high-frequency options (Babylog 8000, Infant Star, Stephanie) and an exclusive high-frequency oscillator (SensorMedics 3100A). MEASUREMENTS: Noise levels were recorded by a microphone and measured by a decibel recording device at a defined distance from a test lung. RESULTS: Noise levels were highest for the SensorMedics and the Babylog (70 dB and 62 dB, respectively). Whereas the SensorMedics increased noise production with amplitude, the Babylog remained at a constant level. The Infant Star (52 dB) and the Stephanie (54 dB) were significantly less noisy at their maximum levels of amplitude (40 mbar and 50 mbar, respectively). CONCLUSION: Most levels recorded were below those measured within an incubator without the use of a ventilator. We conclude that neonatal high-frequency ventilators do not represent a major contribution to noise levels for newborns in neonatal intensive care units (NICUs).

Decrease in lung volume depends on end-expiratory pressure in a rabbit model of airway lavage.

BACKGROUND: In the past, the rabbit model of repeated airway lavage has been extensively used to induce a decrease in lung volume accompanied by impairment in lung mechanics and gas exchange. OBJECTIVES: The rationale of our study was to investigate the influence of different end-expiratory pressure (EEP) levels (0.4-4.2 cm H2O) on changes in functional residual capacity (FRC) and the efficacy of lavages administered. METHODS: Forty-five rabbits were subjected to 2-8 lavages with 20 ml/kg warm normal saline until arterial/alveolar oxygen tension (a/A ratio) had decreased to

[Efficiency and risk of chest physiotherapy in the newborn--review of the literature]. / Effizienz und Risiken der Atemphysiotherapie beim Neugeborenen--Ubersicht über die Literatur.

Chest physiotherapy (CP) in the mechanically ventilated newborn infant belongs to standard treatment methods of neonatal intensive care units in many countries for more than twenty years. In the late seventies, some of the studies published were able to demonstrate a beneficial effect of CP on short time improvement of oxygenation in those newborns treated. Other trials dealt with the (patho)-physiologic changes e.g. in cerebral perfusion following routine nursery procedures such as positioning, suctioning and CP. Recent studies have shown that the mechanically ventilated preterm infant is at risk to suffer intracranial bleeding or a "postnatal encephaloclastic porencephaly" due to routine CP. Prospective randomized trials with large patient numbers are needed to prove an effect of CP on shortening mechanical ventilation in the newborn. Meanwhile CP should not be administered on a routine basis especially not in the preterm infant, but only after assessment of the individual risk-benefit-ratio.

Fatal rupture of a sacrococcygeal teratoma during delivery.

We report the case of premature infant born at 32 weeks' gestation with a sacrococcygeal teratoma diagnosed in utero. During delivery by cesarean section, profound bleeding due to rupture of the teratoma occurred. Despite volume expansion with saline, albumin, and whole blood, a satisfactory peripheral perfusion of the infant was only briefly achieved. Surgical intervention to stop the bleeding was unsuccessful. Resuscitation of the infant was discontinued after 55 minutes. The relevant literature is discussed, and suggestions for the management of infants with sacrococcygeal teratomas are made.

Partial transsection of the neonatal trachea.

This report describes an unusual case of partial transsection of the neonatal trachea after intubation. Mucosal injury led to the formation of a balloon-shaped, air-filled cyst that did not allow ventilation of the airways either via a tracheal tube or with a face mask. Several minutes after death, the cyst had collapsed and bag and mask ventilation produced adequate chest movements.

Effect of inhaled nitric oxide on intrapulmonary right-to-left-shunting in two rabbit models of saline lavage induced surfactant deficiency and meconium instillation.

Marked hypoxia secondary to intrapulmonary right-to-left shunting is a characteristic of respiratory failure in human neonates and can sometimes be complicated by additional extrapulmonary right-to-left shunting. To investigate the effect of inhaled nitric oxide (iNO) on intrapulmonary shunting, two typical pulmonary diseases of the newborn (respiratory distress syndrome and meconium aspiration) were reproduced in 32 mechanically ventilated rabbits weighing approximately 2 kg each. After tracheotomy, catheters were inserted into a jugular vein, a carotid artery and the right ventricle (to measure systolic right ventricular pressure [SRVP] and mixed venous oxygen content for calculation of shunt by Fick equation). Repeated airway lavages (LAV) with normal saline or repeated instillations of a suspension of human meconium (MEC) were continued until both the a/A-ratio was < or =0.14 and a peak inspiratory pressure > or =22 mbar was needed to keep the tidal volume constant at 10 ml/kg of body weight. Measurements of shunt, SRVP, systolic systemic pressure, physiological dead space, tidal volume and a ventilation index were performed before and after completion of lung damage and at 20 and 60 min after administering iNO at 80 ppm. Four groups of rabbits were studied (n=8 in each group): LAV control and intervention, Mec control and intervention. 60 min after starting iNO, there was a decrease in shunt (LAV: 67.6%+/-[SD] 11.3% vs 56.2+/-16.4, P=0.05; MEC: 52.6+/-6.3 vs 44.3+/-8.3, P < 0.05), in SRVP (LAV: 29.7 mmHg +/-10.1 mmHg vs 20.0+/-8.2, P < 0.01; MEC: 25.1+/-4.4 vs 22.3+/-5.0, P=0.46) and in dead space (% of tidal volume, LAV: 32.7%+/-10.5% vs 25.9+/-10.1, P < 0.01; MEC: 26.1+/-16.6 vs 18.9+/-10.1, P=0.05). These results demonstrate that iNO decreases intrapulmonary shunt (as well as SRVP and dead space). We suggest that iNO may be beneficial in human newborns with severe respiratory failure even if no extrapulmonary shunting via ductus or foramen ovale is apparent.

Enhancement of surfactant effect by a mechanical volume recruitment maneuver depends on the lungs preexisting distension.

'Rescue' surfactant treatment of premature infants with respiratory distress syndrome (RDS) results in two mechanisms: stabilization of alveoli already being ventilated and recruitment of alveoli collapsed before surfactant administration. Mechanical recruitment of alveoli from this collapsed compartment might enhance the immediate effects of surfactant treatment. To test this hypothesis 15 mechanically ventilated young rabbits underwent repeated airway lavage with normal saline at a constant, positive end-expiratory pressure (PEEP) of 3 cm H2O until both the a/A ratio was < 0.12 and a peak inspiratory pressure (PIP) > 20 mbar was needed to keep the tidal volume (VT) at 10 ml/kg. Surfactant (Survanta) was given over 4 min in conjunction with a mechanical volume recruitment maneuver (VRM) which consisted of an increased PIP by 33% of baseline values. The effects of surfactant were assessed using two indices of gas exchange (a/A ratio and PaCO2), four indices of lung function (functional residual capacity, FRC, dynamic lung compliance, Crs, VT and the alveolar portion of VT) and postmortem pressure-volume curves and were compared with two groups of rabbits receiving surfactant alone or no surfactant at all. VRM yielded an increase in Crs by +22% whereas VT increased by +58% suggesting overdistension of terminal airways to some extent. There were no differences between the surfactant and the VRM + surfactant groups for all indices assessed after an observational period of 2 h following surfactant administration. In a previous model using a PEEP of 1 cm H2O [Krause et al., Am J Respir Crit Care Med 1997;156:862-866], significant differences have been disclosed for Crs, VT and FRC. In conclusion, the enhancement of surfactant effect by VRM largely depends on the preexisting distension of the lungs.

Rate of surfactant administration influences lung function and gas exchange in a surfactant-deficient rabbit model.

The aim of this study was to test whether the effect of surfactant treatment on lung function in a surfactant-deficient animal model can be influenced by the rate at which surfactant is administered. Surfactant deficiency was induced in 18 New Zealand white rabbits (weighing approx. 1 kg each) by lung lavage with normal saline. The arterial/alveolar oxygen ratio (a/A ratio), functional residual capacity (FRC), dynamic compliance of the respiratory system (Crs), tidal volume (V(T)), alveolar portion of the tidal volume (V(A)) and arterial P(CO2) (P(a,CO2)) were measured before and after lavage and 15, 30, 60, 90, and 120 min after administration of a single dose of surfactant (Survanta, 100 mg/kg). Two surfactant administration protocols were compared over a 2-h interval: an infusion lasting 4 min and an infusion over 2 min. Both administrations were given during continuous mechanical ventilation. The six lung function and gas exchange parameters improved significantly following surfactant administration over 2 min compared with a control group. However, only the a/A ratio and V(A) improved following the 4-min protocol. Comparison of the two intervention protocols yielded significantly differences in V(A) and P(a,CO2), favoring the shorter administration. These results support the hypothesis that fast (2 min) administration of surfactant will improve its distribution to formerly collapsed alveoli and results in better lung function, improved ventilation, and (to a lesser extent) better oxygenation than prolonged infusions (4 min).