Philip C. Etches

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.

Eight-year school performance and growth of preterm, small for gestational age infants: a comparative study with subjects matched for birth weight or for gestational age.

Eight-year school performance and growth outcome are reported for three groups of preterm infants: one group that was small for gestational age (SGA; 36 infants) and two comparison groups that were appropriate in size for gestational age, one matched for birth weight and the other for gestational age. The subjects all had white parents whose mother tongue was English and were matched for gender, mothers height, mothers education, and fathers socioeconomic status (Blishen Scale). A comparison peer group of term infants was also studied. The three preterm groups did not differ in school performance or physical growth, with the exception of head circumference, which was smaller in the SGA children. All preterm groups had growth measures, intellectual and visual-motor integration scores, reading and arithmetic grade levels, and behavior rating levels significantly inferior to those of the peer group. Receptive vocabulary scores and spelling grade levels did not differ between the preterm groups and the peer group. On multivariate analyses, mothers education was the primary predictor of academic grade levels for the preterm SGA group, and the only predictor when the disabled children were excluded from analyses. Preterm SGA children without disabilities had academic scores similar to those of their term peers, but their scores indicated more hyperactivity. Intrauterine growth retardation did not appear to impose a disadvantage on the preterm children in this study.

Ototoxic drugs and sensorineural hearing loss following severe neonatal respiratory failure

AIM To determine relationships between ototoxic drugs and 4-y sensorineural hearing loss (SNHL) in near-term and term survivors of severe neonatal respiratory failure. METHODS All 81 survivors of the Canadian arm of the Neonatal Inhaled Nitric Oxide Study (mortality 32, loss to follow-up 9) received loop diuretics, aminoglycosides, and neuromuscular blockers (NMB), and 50 received vancomycin as neonates. Prospective, longitudinal secondary outcome using audiological tests diagnosed late-onset, progressive SNHL in 43 (53%); not flat (sloping) in 29, flat (severe to profound) in 14. Risk for SNHL was determined. RESULTS A combination of duration of diuretic use of >14 d and average NMB dose of >0.96 mg/kg/d contributed to SNHL among survivors (odds ratio 5.2; 95% CI 1.6, 16.7). Markers of illness severity did not contribute. Dosage or duration of aminoglycosides use did not relate to SNHL. Cumulative dosages and duration of use of diuretics; NMB; use of vancomycin; and overlap of diuretics with NMB, aminoglycosides, and vancomycin individually linked to SNHL (p<0.001). CONCLUSION Overuse of loop diuretics and/or NMB contributes to SNHL after neonatal respiratory failure; markers of illness severity or the appropriate administration of aminoglycosides do not.

Before viability : A geographically based outcome study of infants weighing 500 grams or less at birth

Objective. The primary objective of this study was to determine the likelihood of long-term survival and avoidance of disabilities in a geographically based population of infants born at 20 weeks gestation or more and weighing 500 g or less at birth. Study Design. This was a 12-year historical cohort follow-up study of all infants born in this gestational age and birth weight category in the Province of Alberta, Canada, between 1983 and 1994. Data were collected from certificates of live births or stillbirths, death certificates, hospital records, and longitudinal multidisciplinary follow-up examinations. Results. One thousand one hundred ninety-three infants were of 20 weeks gestation or more, weighed 500 g or less, and were born between 1983 and 1994. Eight hundred eleven (68.0%) were stillborn and 382 (32.0%) were born alive. Among the latter, neonatal intensive care was provided in 113 (29.6%) and withheld in 269 (70.4%). The infants receiving intensive care were of heavier birth weight, later gestational age, higher antenatal risk scores, were more likely to be born in a level III center, to have received antenatal steroids, and to have been delivered by cesarean section. Of the infants receiving intensive care, 95 (84.1%) died and 18 (15.9%) were discharged alive, but 5 of these died after discharge because of respiratory complications. The infants discharged alive had later gestational age, were more likely to be small for gestational age, singletons, treated with antenatal steroids, and to have been delivered by cesarean section. Maternal indications were described in the majority of cesarean sections done for live-born infants. The 13 infants who were long-term survivors were followed at ages 12 and 36 months adjusted age. Four had no serious disabilities, 4 had one disability (cerebral palsy or mental retardation), and 5 had multiple disabilities (cerebral palsy plus mental retardation with blindness in 2 cases and deafness in 1 case). Conclusion. The majority of infants born at gestational age 20 weeks or more weighing <500 g were stillborn. Among live births, neonatal intensive care was withheld in 70% and initiated in 30%. Of the latter, 11% survived to 36 months of age, and of these, 4 infants (31%), most of whom are small for gestational age, female infants, avoided major disabilities but 9 (69%) had one or more major disabilities. Survivors are prone to rehospitalizations early in life, slow growth, feeding problems, and minor visual difficulties; rates of learning-related and behavioral problems at school age are not yet known. Implications. Parents and caregivers faced with the impending delivery of an infant in this gestational age/birth weight category should understand that survival without multiple major disabilities is possible but rare. They should be made aware of local population-based results and not just isolated reports.

Late-onset, progressive sensorineural hearing loss after severe neonatal respiratory failure.

Objectives To determine the prevalence of sensorineural hearing loss (SNHL) at the age of 4 years among survivors of severe neonatal respiratory failure with and without congenital diaphragmatic hernia and to document the occurrence of late-onset or progressive SNHL among the survivors. Design Prospective, longitudinal secondary outcome study. Setting Multicenter Canadian study in 9 tertiary referral centers. Patients Eighty-one (89%) of ninety 4-year-old survivors born from 1994 to 1996 of ≥34 weeks gestation at birth with severe neonatal respiratory failure (2 oxygenation indices ≥25 at least 15 minutes apart). Main Outcome Measures Repeated audiologic measurements from birth to the age of 4 years with documentation of the entire cohort at 2 and 4 years of age. Results Forty-three (53%) of 81 tested 4-year-old survivors had SNHL; 28 (42%) of 66 without congenital diaphragmatic hernia and 15 (100%) of 15 with congenital diaphragmatic hernia. High-frequency SNHL occurred in 65% of the patients. Of the 43 children with SNHL at 4 years, 30 (70%) had loss at 2 years, and 18 (60%) of these 30 had progressive loss between 2 and 4 years of age. For 13 children with SNHL onset after 2 years of age, the loss was less severe with lesser involvement of the lower frequencies. Conclusion Survivors of severe neonatal respiratory failure frequently develop late-onset SNHL that may be progressive. Urgent investigation is required to enable further understanding and prevention of this problem. Severe neonatal respiratory failure should be an indication for long-term audiologic surveillance.

Nitric Oxide Reverses Acute Hypoxic Pulmonary Hypertension in the Newborn Piglet

ABSTRACT: Inhaled nitric oxide has been reported to act as a specific pulmonary vasodilator. We used the newborn piglet to create acute hypoxic pulmonary hypertension and examined the effect of inhaled nitric oxide in this model. Six newborn piglets were instrumented in order to measure cardiac index, pulmonary arterial pressure, and systemic arterial pressure. Pulmonary hypertension was induced by reducing the fraction of inspired oxygen to 0.12 to 0.14. With hypoxia (arterial oxygen saturation between 35 and 45%), pulmonary arterial pressure increased by 48% (p < 0.01), pulmonary vascular resistance increased by 74% (p < 0.01), and both systemic arterial pressure and systemic vascular resistance decreased by 38 and 31%, respectively (p < 0.01). The animals were then giving varying concentrations of inhaled nitric oxide between 5 and 80 parts per million in random order. All concentrations of nitric oxide were associated with a rapid decrease in pulmonary arterial pressure and pulmonary vascular resistance (p < 0.001). Cardiac index increased (p < 0.001) and systemic vascular resistance significantly decreased (p = 0.01) with all doses of inhaled nitric oxide. The ratio of pulmonary to systemic vascular resistance decreased with all levels of inhaled nitric oxide (p < 0.001). For all of the above observations there was no significant difference noted between the varying doses of nitric oxide. The time course of the pulmonary arterial pressure response to nitric oxide was approximately twice as fast as that seen with the inhalation of 100% oxygen (10, 50, 90% responses of 4.1, 8.8, 88.6 versus 6.7, 51.9, 197 s, respectively; p < 0.01). Inhaled nitric oxide at levels of 5 parts per million or greater reverses hypoxia-induced pulmonary vasoconstriction in the newborn piglet model.

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.

Outcome of shunted posthemorrhagic hydrocephalus in premature infants

Patient histories of 29 infants were reviewed whose birth weights were less than 2,000 gm and who had received ventricular shunts in the neonatal period for posthemorrhagic hydrocephalus. This procedure was performed at a time when routine screening of low birth weight infants for intracranial hemorrhage was not undertaken and serial lumbar puncture usually was not employed. The overall outcome was poor, with 62% of shunted infants either dying or surviving with moderate or severe handicap. Neurodevelopmental outcome was associated with the interval between the diagnosis of hydrocephalus and shunting; an adverse outcome was associated with an increased interval. Current practices for treating posthemorrhagic hydrocephalus are discussed.

Management and outcome of positive urine cultures in a neonatal intensive care unit

OBJECTIVES The aim of this study was to describe the management and outcome of positive urine cultures in a neonatal intensive care unit (NICU). STUDY DESIGN A chart review was completed of infants born October 1, 2004 to December 31, 2006 and admitted to the NICU at the Royal Alexandra Hospital, Edmonton, Alberta with any growth of bacteria or fungi in urine. RESULTS Positive urine cultures were obtained in 64 of 2936 admissions (2%) and were classified as contaminated urines (n=34), possible urinary tract infection (UTI) (n=14), definite UTI (n=10), and candidal UTI (n=6). Management was inconsistent. Two children required new assisted ventilation but no other complications occurred. CONCLUSIONS The diagnosis of UTI in NICU is hampered by use of urine collection methods that are subject to contamination. Outcome is generally excellent, but there is a great need for guidelines on management of positive urine cultures in the NICU.