Non-invasive inhaled nitric oxide in the treatment of hypoxemic respiratory failure in term and preterm infants.

OBJECTIVES: Inhaled nitric oxide (iNO) is effective in conjunction with tracheal intubation (TI) and mechanical ventilation (MV) for treating arterial pulmonary hypertension and hypoxemic respiratory failure (HRF) in near-term and term newborns. Non-invasive respiratory support with nasal continuous positive airway pressure (CPAP) is increasingly used to avoid morbidity associated with TI and MV, yet the effectiveness of iNO delivery via nasal CPAP remains unknown. To evaluate the effectiveness of iNO delivered via the bubble nasal CPAP system in term and preterm newborns with HRF. STUDY DESIGN: Electronic medical records from all infants admitted to the neonatal intensive care unit (NICU) during 2005 to 2014 (n=10, 895) were screened for treatment with iNO therapy for HRF. Detailed data on population characteristics and cardiorespiratory, iNO and respiratory support indices were abstracted for all infants, who were administered iNO non-invasively using bubble nasal CPAP. Change in relevant indices at baseline (before initiating non-invasive iNO) and at 3, 6, 12 and 24 h after non-invasive iNO therapy were analyzed using repeated measures analysis of variance. RESULTS: Of 795 infants treated with iNO (7.3% of total NICU admissions) over a 10-year period, 107 infants (13.4% of iNO treated) with birth weight 2448±1112 g and gestational age 35.3±5.8 weeks received iNO non-invasively. 25 infants received iNO exclusively non-invasively, whereas in remaining 82 infants non-invasive route followed invasive delivery via TI and MV. Indications for using non-invasive iNO included idiopathic pulmonary hypertension (39%), congenital heart disease (37%), bronchopulmonary dysplasia (10%), meconium aspiration syndrome (9%) and congenital diaphragmatic hernia (5%). Over the 24 h following initiation of non-invasive iNO, fractional oxygen requirements decreased (0.38 to 0.32; P<0.0005) and SpO2 increased (90.7 to 91.6%; P<0.01) with no significant changes in heart rate, respiratory rate, blood pressure, pH and PaCO2. On average non-invasive iNO was initiated on day of life 9 with a maximal dose was 20 p.p.m. The average duration of iNO therapy and the duration over which it was weaned off were 134 and 51 h, respectively. Analysis of environmental gases during non-invasive iNO therapy revealed median ambient nitrogen dioxide and nitric oxide levels of 0.30 and 0.01 p.p.m., respectively. CONCLUSIONS: Initiation of iNO in infants on bubble nasal CPAP or continuation of iNO in infants transitioning from MV to bubble nasal CPAP is associated with improved oxygenation during HRF in term and preterm infants. Non-invasive iNO may have a synergistic effect with airway recruitment strategies such as nasal CPAP.

Randomised controlled trial of thiopental for intubation in neonates.

AIMS: To determine the effects of premedication with thiopental on heart rate, blood pressure, and oxygen saturation during semi-elective nasotracheal intubation in neonates. METHODS: A randomised, placebo controlled, non-blinded study design was used to study 30 neonates (mean birthweight 3.27 kg) requiring semi-elective nasotracheal intubation. The babies were randomly allocated to receive either 6 mg/kg of thiopental (study group) or an equivalent volume of physiological saline (control group) one minute before the start of the procedure. Six infants were intubated primarily and 24 were changed from orotracheal to a nasotracheal tube. The electrocardiogram, arterial pressure wave, and transcutaneous oxygen saturation were recorded continuously 10 minutes before, during, and 20 minutes after intubation. Minute by minute measurements of heart rate, heart rate variability, mean blood pressure (MBP) and transcutaneous oxygen saturation (SpO(2)) were computed. The differences for all of these between the baseline measurements and those made during and after intubation were determined. Differences in the measurements made in the study and the control groups were compared using Student's t test. RESULTS: During intubation, heart rate increased to a greater degree (12.0 vs -0.5 beats per minute, p < 0.03) and MBP increased to a lesser degree (-2.9 vs 4.4 mm Hg; p < 0.002) in the infants who were premedicated with thiopental. After intubation only the changes in MBP differed significantly between the two groups (-3.8 vs 4.6 mm Hg; p < 0.001). There were no significant changes in the oxygen saturation between the two groups during or after intubation. The time taken for intubation was significantly shorter in the study group (p < 0.04). CONCLUSIONS: The heart rate and blood pressure of infants who are premedicated with thiopental are maintained nearer to baseline values than those of similar infants who receive no premedication. Whether this lessening of the acute drop in the heart rate and increase in blood pressure typically seen during intubation of unmedicated infants is associated with long term advantages to the infants remains to be determined.

Spontaneous correction of the malpositioned percutaneous central venous line in infants.

Malpositioning of the percutaneously placed central venous line (PCVL) or percutaneously inserted central catheter (PICC) in infants is not a rare occurrence. It has been occasionally observed that these lines spontaneously correct themselves. This prospective study was done to study the incidence of malposition and spontaneous correction. Using a modification of the standard method, 187 catheters were placed with 98.9 % success. Seven of these were initially malpositioned. All seven corrected themselves within a day when left in and used as a peripheral intravenous line. In many centers malpositioned catheters are taken out and replaced, which imposes great stress on the critically ill infant. Our study suggests that to avoid this stress the catheter should be left in place, since spontaneous correction may occur.

Continuous positive airway pressure (CPAP).

Progress in neonatal intensive care is closely linked to improvements in the management of respiratory failure in small infants. This applies to the care of the preterm infants with immature lungs, and also to treatment of the preterm or full term infants with specific diseases that are associated with respiratory failure. Respiratory distress of the newborn continues to account for significant morbidity in the intensive care unit. The spectrum of disease ranges from mild distress to severe respiratory failure requiring varying degrees of support. The current modalities of ventilatory assistance range from the more benign continuous positive airway pressure (CPAP) to conventional mechanical ventilation, and on to high frequency ventilation. It is a reasonable supposition that the type of ventilatory assistance provided to these infants should be graded according to the severity of the disease. However, the principal objective in selecting the mode of respiratory support should be to use a modality which results in minimal volo- or barotrauma to the infant. The following detailed description on CPAP explains its physiological effects, delivery system, indications for use, application, maintenance, and associated complications. The equipment described is simple to use, has a greater cost benefit, and has a more universal application, which is of help to smaller units including those in the developing parts of the world. We have also included our institutional clinical experience of CPAP usage in very low birth weight infants from the periods before and after commercial availability of surfactant in the United States.

Weaning strategy with inhaled nitric oxide treatment in persistent pulmonary hypertension of the newborn.

AIM: To determine if infants who had become dependent on inhaled nitric oxide treatment could be successfully weaned off it if FIO2 was increased briefly during withdrawal. METHODS: Sixteen infants admitted for conditions associated with increased pulmonary vascular resistance responded well to inhaled nitric oxide treatment with a significant increase in PaO2 (maximum inhaled nitric oxide given 25 ppm). Weaning from inhaled nitric oxide in 5 ppm decrements was initiated once the FIO2 requirement was less than 0.5. When patients were stable on 5 ppm of inhaled nitric oxide, the gas was then discontinued. If a patient showed inhaled nitric oxide dependence-that is, oxygen saturation fell by more than 10% or below 85%-inhaled nitric oxide was reinstated at 5 ppm and the patient allowed to stabilise for 30 minutes. At this time, FIO2 was increased by 0.40 and weaning from inhaled nitric oxide was attempted again. RESULTS: Nine infants were successfully weaned on the first attempt. The seven infants who failed the initial trial were all successfully weaned following the increase in FIO2. After successful weaning, FIO2 was returned to the pre-weaning level in mean 148(SD 51) minutes and inhaled nitric oxide was never reinstated. CONCLUSION: Infants showing inhaled nitric oxide dependency can be successfully weaned by increasing FIO2 transiently.

Preoperative cardiorespiratory trends in infants with congenital diaphragmatic hernia.

The objective of this study was to determine the cardiovascular and pulmonary adaptations of infants with congenital diaphragmatic hernia (CDH) from birth until delayed surgery through the use of continuous monitoring. Continuous cardiovascular (HR, heart rate variability [HR-SD], BP, blood pressure variability [BP-SD], and oxygen saturation) and ventilatory (minute volume, airway pressure, and effective compliance) measurements were made on-line, using a computerized whole-body plethysmograph-incubator (Vital-trends, VT1000), in nine ventilated infants with CDH. Data collection commenced at birth and continued until surgery. Minute mean values for each variable were recorded. Hourly means were computed from the minute means, averaged across infants each hour over the first 50 hours of life, and regressed against postnatal age. Results showed a significant increase in BP (P < .01), BP-SD (P < .05), HR-SD (P < .04), and pH (P < .02) versus postnatal age, and a decrease in PaCO2 (P < .04), FIO2 (P < .001), Alveolar-arterial oxygen gradient (P < .003), and oxygenation index (P < .002). Infants with CDH show cardiopulmonary trends over the first 2 days of life that are qualitatively similar to those of normal newborn infants. Deviation from these idealized patterns may identify an infant who is not responding satisfactorily to the given therapy and who may require alternative treatment modalities.

Congenital diaphragmatic hernia: survival treated with very delayed surgery, spontaneous respiration, and no chest tube.

This report suggests that stabilization of the intrauterine to extrauterine transitional circulation combined with a respiratory care strategy that avoids pulmonary overdistension, takes advantage of inherent biological cardiorespiratory mechanics, and very delayed surgery for congenital diaphragmatic hernia results in improved survival and decreases the need for extracorporeal membrane oxygenation (ECMO). This retrospective review of a 10-year experience in which the respiratory care strategy, ECMO availability, and technique of surgical repair remained essentially constant describes the evolution of this method of management of congenital diaphragmatic hernia.

Effect of blood pressure cuffs on neonatal circulation: their potential application to newborns with persistent pulmonary hypertension.

The contribution of vasoactive pharmacologic agents to the care of the infant with primary pulmonary hypertension of the newborn (PPHN) is hampered by their limited ability to act selectively on different vascular beds. In contrast, blood pressure (BP) cuffs decrease flow and increase resistance only in the extremities around which they are applied. They therefore offer a means of increasing systemic vascular resistance without affecting pulmonary vascular resistance, a hemodynamic effect that may be particularly desirable among PPHN patients receiving vasodilators. We studied the effect of BP cuffs on the circulation of nine healthy neonates and three infants with severe PPHN. Among the healthy neonates, inflation of the cuffs to 20 mmHg had no discernible hemodynamic effect. Inflation to systolic pressures, however, caused the left ventricular preejection period to increase from 36 +/- 9 ms to 45 +/- 10 ms, the end-diastolic dimension to increase from 1.80 +/- 0.16 cm to 1.92 +/- 0.16 cm, and the cardiac output to fall to 87 +/- 12% of baseline (all p < 0.05)--changes indicative of an increase in systemic vascular resistance. Application of BP cuffs to the patients with PPHN was associated with 10-25 mmHg increases in transcutaneous arterial oxygen tensions. Administration of tolazoline to these patients while the cuffs were inflated resulted in additional 10-20 mmHg increases and did not precipitate hypotension. These observations suggest that BP cuffs can play a useful role in the management of patients with PPHN.

Hearing and neurodevelopmental outcome in survivors of persistent pulmonary hypertension of the newborn.

Thirty-four infants who had a diagnosis of severe persistent pulmonary hypertension of the newborn at birth (alveolar-arterial oxygen difference greater than 600) were treated without paralysis or hyperventilation to induce alkalosis. All survived. Twenty-seven of these 34 eligible infants (79%) underwent neurologic, intelligence, and audiologic testing between 10 months and 6 years of age. Children who were younger than 1 year of age at the initial hearing test were retested after they reached 2 years of age. The average IQ was within the normal range (mean = 96.23). None had sensorineural hearing loss. Severe neurologic abnormalities were seen in 4 children, 3 of whom had been severely asphyxiated at birth (determined by biochemical criteria). Mild neurologic abnormalities were observed in 5 children. Two infants had bronchopulmonary dysplasia because they required supplemental oxygen for 29 and 66 days, respectively, and had abnormal chest roentgenograms; 1 patient takes intermittent doses of albuterol (Ventolin) and neither currently requires supplemental oxygen. This study of 27 infants with severe persistent pulmonary hypertension of the newborn suggests that conservative management without induced alkalosis or respiratory paralysis is accompanied by no sensorineural hearing loss and a good neurologic outcome.

Benign gaseous distension of the bowel in premature infants treated with nasal continuous airway pressure: a study of contributing factors.

Continuous positive airway pressure (CPAP) administered as a mixture of oxygen and compressed air via nasal prongs has dramatically improved survival rates and lessened the frequency of barotrauma and bronchopulmonary dysplasia in the premature infant with respiratory distress syndrome. Associated with the increased use of nasal CPAP has been the development of marked bowel distension (CPAP belly syndrome), which occurs as the infant's respiratory status improves and the baby becomes more vigorous. To identify contributing factors, we prospectively compared 25 premature infants treated with nasal CPAP with 29 premature infants not treated with nasal CPAP. Infants were followed up for development of distension, defined clinically as bulging flanks, increased abdominal girth, and visibly dilated intestinal loops. We evaluated birth weight, weight at time of distension, method of feeding (oral, orogastric tube), and treatment with nasal CPAP and correlated these factors with radiologic findings. Of the infants who received nasal CPAP therapy, gaseous bowel distension developed in 83% (10/12) of infants weighing less than 1000 g, but in only 14% (2/14) of those weighing at least 1000 g. Only 10% (3/29) of infants not treated with nasal CPAP had distension, and all three weighed less than 1000 g. Presence of sepsis and method of feeding did not correlate with occurrence of distension. Neither necrotizing enterocolitis nor bowel obstruction developed in any of the patients with a diagnosis of CPAP belly syndrome. Our study shows that nasal CPAP, aerophagia, and immaturity of bowel motility in very small infants were the major contributors to the development of benign gaseous bowel distension.

Right pneumonectomy syndrome: a lethal complication of lung resection in a newborn with cystic adenomatoid malformation.

A newborn girl underwent a right pneumonectomy for cystic adenomatoid malformation. She subsequently developed compression of the trachea and left mainstem bronchus by a combination of aortic arch, pulmonary artery, and ductus arteriosus. She died while planning aortic suspension, and the anatomic relationships were confirmed by autopsy. This problem is potentially treatable by a variety of means.

Experience with percutaneous indwelling peripheral arterial catheterization in neonates.

We present an experience with indwelling peripheral arterial catheters in preterm and term neonates. During a 12-month interval, 158 peripheral arterial lines were inserted in 115 infants. Eighty-eight infants required a single line while 27 infants required more than one line. Ninety-one catheters (57.6%) were electively removed, and 67 (42.4%) had to be discontinued prematurely. Vessels used included 110 radial arteries (69.6%), 27 posterior tibial arteries (17.1%), and 21 temporal arteries (13.3%). There were only two major complications (1.27%), both related to infections. The technique is described in detail. In our experience, with appropriate precaution, peripheral arterial cannulation has been a safe and reliable alternative to umbilical arterial catheterization.

Retrocardiac pneumomediastinum in association with tracheal and esophageal perforations.

Retrocardiac pneumomediastinum was encountered in two premature infants; one had a tracheal perforation and one an esophageal perforation. Contrast studies showed communication between the sites of perforation and the retrocardiac air. Clinical signs suggestive of such perforation include abnormal course of tubes on plain chest films and bloody aspirates.

Management of infants with severe respiratory failure and persistence of the fetal circulation, without hyperventilation.

The successful management of 15 infants suffering from persistence of fetal pulmonary circulation and in severe respiratory failure is presented. The treatment regimen focused on minimizing barotrauma. Infants were intubated nasotracheally and ventilated with intermittent mandatory ventilation. Peak inspiratory pressures were determined by the clinical assessment of chest excursion. Ventilator settings and fractional inspiratory oxygen (FiO2) were selected to maintain a PaO2 between 50 and 70 mm Hg; PaCO2 was not a controlling parameter and was allowed to increase as high as 60 mm Hg. Hyperventilation and muscle relaxants were not used. High ventilator rate was used in ten infants who required high inspiratory pressure to maintain chest excursion, with a favorable response in five. Tolazoline was given to 14 infants of whom ten showed an improvement in oxygenation; dopamine was given to three infants who were oliguric. All infants survived, and only one infant developed chronic lung disease which was defined by the infant's need for supplemental oxygen beyond 30 days of life.

Complete cartilage-ring tracheal stenosis associated with anomalous left pulmonary artery: the ring-sling complex.

The persistent high mortality in infants with pulmonary artery "sling" (retrotracheal anomalous left pulmonary artery) is primarily due to the coexistence in such patients of long-segment tracheal stenosis due to complete cartilage rings. Five such patients are reported. Airway studies (by filtered high-kV radiography, bronchography, and/or CT) showed low carina, horizontal equal-length right and left mainstem bronchi, and long-segment tracheal stenosis. The length of the stenosis far exceeded the contact with the pulmonary sling. The suggested term "ring-sling complex" for such patients correctly places emphasis on detection of the tracheal malformation, which currently has no satisfactory surgical treatment.