Anne J. Tierney

Inhaled nitric oxide in infants referred for extracorporeal membrane oxygenation: Dose response☆☆☆★

To determine the role of inhaled nitric oxide (NO) in a population of critically ill hypoxic near-term infants and to determine the dose response to inhaled NO, we examined a consecutive group of 23 infants referred for neonatal extracorporeal membrane oxygenation (ECMO) who had an oxygen index of 20 or greater after treatment with bovine surfactant. Inhaled NO was administered in concentrations from 5 to 80 ppm in random order to 23 infants. Overall, 13 infants had a significant response (an improvement in arterial oxygen pressure > 10 mm Hg or arterial oxygen saturation > 10%) to the first administration of inhaled NO, and one infant had a late response. There was no significant difference in the response to inhaled NO as measured by changes in arterial oxygen pressure or in the alveolar-arterial difference in partial pressure of oxygen, for any of the doses from 5 to 80 ppm. Thirteen infants had echocardiographic evidence of persisted pulmonary hypertension; 11 of these infants responded, compared with 3 responders among the 10 infants without persistent pulmonary hypertension of the newborn (p < 0.01). Overall, 11 infants required ECMO; there were two deaths in this group. Seven infants had congenital diaphragmatic hernia; five of those had a response to NO inhalation and four required ECMO. Our study demonstrates that there is no significant difference in response between low and high doses of inhaled NO and that this treatment may prevent the need for ECMO in some infants referred for this therapy, especially in infants with pulmonary hypertension. Prospective, controlled, randomized, and blinded trials of low doses of inhaled NO are needed to determine the clinical role of this potentially useful therapy.

Inhaled nitric oxide for premature infants after prolonged rupture of the membranes.

We evaluated the use of inhaled nitric oxide in eight premature infants (520 to 1440 gm, 24 to 31 weeks of gestation) who failed to respond to conventional management and who had prolonged rupture of the membranes and oligohydramnios. All infants had a significant improvement in oxygenation and a fall in mean airway pressure with inhaled nitric oxide. Further studies are required to determine the safety and efficacy of this form of therapy.

Timing of repair of congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation support

Treatment of congenital diaphragmatic hernia (CDH) has undergone a revolutionary change in philosophy, from previous urgent repair to the present practice of stabilization and delayed repair. However, when extracorporeal membrane oxygenation (ECMO) is required, many people believe that the risk of postoperative pulmonary hypertension (PPHN) mandates hernia repair while on ECMO. This report details the experience in two ECMO centers with stabilization, ECMO if required, and CDH repair post-ECMO. All CDH patients symptomatic in the first hour of life with a gestational age of at least 34 weeks during the period were reviewed retrospectively. Standard criteria were used to select patients for ECMO. High-frequency jet or oscillating ventilators and nitric oxide were not routinely available throughout the study period, but were used in some of the more recent patients. A total of 60 patients presented to the two centers; 24 cases were stabilized with conventional management, repair of the CDH was done elective, and survival was 100%. Eight patients were referred after having repair elsewhere; six survived (75%). The two deaths were attributable to associated lethal lesions--complex cyanotic heart disease and alveolar capillary dysplasia. Eight patients who required ECMO were managed with the intention of repairing the defect on ECMO. Four survived (50%). Two patients died before repair. Twenty patients were managed with ECMO, with the intention of repairing the defect after decannulation. Overall survival was 13 (65%), deaths were caused by pre-ECMO hypoxia, pulmonary insufficiency, and associated cardiac disease. No patient had recurrent pulmonary hypertension after late repair.(ABSTRACT TRUNCATED AT 250 WORDS)

The dose response of theophylline in the treatment of apnea of prematurity

In an effort to establish the minimum effective dose of theophylline in the treatment of idiopathic apnea of prematurity, a prospective trial of 22 infants with at least 0.33 episodes of apnea per hour were studied. Apnea was diagnosed exclusively by continuous recording of heart rate, respiratory impedance, end-tidal CO2, and either or both transcutaneous oxygen and pulse oximetry. Four discrete serum concentrations of theophylline (23 mumol/l or 4.2 mg/L, 47 mumol/L or 8.5 mg/L, 70 mumol/L or 12.7 mg/L, and 84 mumol/L or 15.3 mg/L) were attained by using repeated loading doses of 4 mg/kg and increasing the maintenance dose from 1 to 1.5 mg/kg to 2 to 2.5 mg/kg, given every 8 hours. Before treatment and 24 hours after each loading dose, airway occlusions and measures of tidal volume, minute ventilation, and respiratory timing were performed. The effectiveness of therapy was assessed by either a continuous computer data-acquisition system or paper recording for the duration of the study. Of the 22 infants, three responded at level 1, three at level 2, and 10 at level 3. One of the four infants loaded to the fourth level had a sustained response for a total cumulative response of 77%. The five remaining infants required additional treatment with doxapram or continuous positive airway pressure. There was a significant increase in inspiratory pressure 100 msec after airway occlusion, maximum inspiratory pressure during airway occlusion, tidal volume, ratio of tidal volume to inspiratory time (mean inspiratory flow), and minute ventilation from the pretreatment measurements to those at the maximum dose of theophylline. The apnea response did not correlate with these improvements in ventilation measures.

Venovenous extracorporeal membrane oxygenation: The effects of proximal internal jugular cannulation

Venovenous (VV) extracorporeal membrane oxygenation (ECMO) using a double lumen catheter has become an accepted method of providing ECMO support for critically ill newborn infants. In addition, use of the cephalic jugular catheter can provide augmented venous blood flow, potentially prevent increased cerebral venous pressure, maintain cerebral venous blood flow, and increase ECMO oxygen delivery. The authors compared their experience using VV double-lumen (VVDL) ECMO with a cephalic jugular catheter with their previous experience using venoarterial (VA) ECMO. They compared 15 infants who had meconium aspiration syndrome (MAS) and 12 who had congenital diaphragmatic hernia (CDH) treated with VVDL ECMO with a cephalic jugular catheter with the same number of infants with each condition treated with VA ECMO (historical controls). There were no significant differences between the groups with respect to birth weights, oxygen indexes before ECMO, of ECMO flows at 4 and 24 hours. For infants with MAS treated with VVDL ECMO, the overall duration of ECMO support was significantly shorter (63 hours VVDLv 118 hours VA; P = .001), and the average cephalic flow was 33 mL/kg for infants treated with VVDL support. For infants with CDH, there were no differences in any of the variables evaluated, including total duration (100 hours VVDLv 128 hours VA; P = .06 [NS]), and the average cephalic flow was 39 mL/kg for infants treated with VVDL support. The venous oxygen content was significantly lower in infants with MAS treated with VVDL ECMO than for historical controls treated with VA ECMO at 4 hours of ECMO support (15.8 v 16.7; P < or = .05). No other significant differences were noted for any of the calculated oxygen transport variables comparing VVDL with VA ECMO infants with CDH treated with VVDL ECMO were extubated sooner than those treated with VA ECMO (10.3 days VVDL v 15.4 days VA; P = 048). In addition, there was no significant difference in the overall incidence of complications or death. This experience suggests that VVDL ECMO using a cephalic jugular catheter results in shorter ECMO runs and provides support that is comparable to VA ECMO for infants with CDH and MAS while avoiding carotid artery cannulation and ligation.

Congenital diaphragmatic hernia: Associated malformations-cystic adenomatoid malformation, extralobular sequestration, and laryngotracheoesophageal cleft: Two case reports

Two infants with unusual bronchopulmonary malformations associated with congenital diaphragmatic hernia (CDH) are presented. One infant had extralobular sequestration and cystic adenomatoid malformation of the lower lobe, in addition to a left-sided CDH. The second infant had a laryngotracheoesophageal cleft extending to the carina (type III) in addition to a left-sided CDH. These associated malformations can have major implications in terms of diagnosis, resuscitation, and surgical management of infants with CDH.