Manuel Durand

Pulse oximetry for continuous oxygen monitoring in sick newborn infants

We studied 54 neonates with acute cardiorespiratory illness and 21 infants with bronchopulmonary dysplasia, to evaluate the accuracy of a nonheated pulse oximeter in predicting arterial oxygen saturation (SaO2). We also studied the accuracy of transcutaneous oxygen tension (tcPO2) in estimating arterial oxygen tension (PaO2) in infants with bronchopulmonary dysplasia. We compared pulse oximeter SaO2 with simultaneously measured SaO2 (range 78% to 100%) using a co-oximeter. Over a wide range of values for heart rate, blood pressure, hematocrit, PO2, PCO2, and pH, linear regression analysis revealed a close correlation between in vivo pulse oximeter readings and in vitro SaO2 measurements in patients with acute (r = 0.86, Y = 29.64 + 0.68X) and chronic (r = 0.91, Y = 6.29 + 0.96X) disease. Regression analysis of tcPO2 versus PaO2 showed an r value of 0.76 in infants with bronchopulmonary dysplasia. In these patients the mean difference between pulse oximeter SaO2 and in vitro SaO2 was 2.9% +/- 1.8% (SD), whereas the mean difference between tcPO2 and PaO2 was -14.5 +/- 11.1 mm Hg. Fetal hemoglobin ranged from 4.3% to 95%. We conclude that pulse oximetry is an appropriate alternative to tcPO2 for continuous oxygen monitoring in newborn infants with acute cardiorespiratory illnesses and chronic lung disease.

Vitamin C Supplementation for Pregnant Smoking Women and Pulmonary Function in Their Newborn Infants: A Randomized Clinical Trial

IMPORTANCE Maternal smoking during pregnancy adversely affects offspring lung development, with lifelong decreases in pulmonary function and increased asthma risk. In a primate model, vitamin C blocked some of the in-utero effects of nicotine on lung development and offspring pulmonary function. OBJECTIVE To determine if newborns of pregnant smokers randomized to receive daily vitamin C would have improved results of pulmonary function tests (PFTs) and decreased wheezing compared with those randomized to placebo. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind trial conducted in 3 sites in the Pacific Northwest between March 2007 and January 2011. One hundred fifty-nine newborns of randomized pregnant smokers (76 vitamin C treated and 83 placebo treated) and 76 newborns of pregnant nonsmokers were studied with newborn PFTs. Follow-up assessment including wheezing was assessed through age 1 year, and PFTs were performed at age 1 year. INTERVENTIONS Pregnant women were randomized to receive vitamin C (500 mg/d) (n = 89) or placebo (n = 90). MAIN OUTCOMES AND MEASURES The primary outcome was measurement of newborn pulmonary function (ratio of the time to peak tidal expiratory flow to expiratory time [TPTEF:TE] and passive respiratory compliance per kilogram [Crs/kg]) within 72 hours of age. Secondary outcomes included incidence of wheezing through age 1 year and PFT results at age 1 year. A subgroup of pregnant smokers and nonsmokers had genotyping performed. RESULTS Newborns of women randomized to vitamin C (n = 76), compared with those randomized to placebo (n = 83), had improved pulmonary function as measured by TPTEF:TE (0.383 vs 0.345 [adjusted 95% CI for difference, 0.011-0.062]; P = .006) and Crs/kg (1.32 vs 1.20 mL/cm H2O/kg [95% CI, 0.02-0.20]; P = .01). Offspring of women randomized to vitamin C had significantly decreased wheezing through age 1 year (15/70 [21%] vs 31/77 [40%]; relative risk, 0.56 [95% CI, 0.33-0.95]; P = .03). There were no significant differences in the 1-year PFT results between the vitamin C and placebo groups. The effect of maternal smoking on newborn lung function was associated with maternal genotype for the α5 nicotinic receptor (rs16969968) (P < .001 for interaction). CONCLUSIONS AND RELEVANCE Supplemental vitamin C taken by pregnant smokers improved newborn PFT results and decreased wheezing through 1 year in the offspring. Vitamin C in pregnant smokers may be an inexpensive and simple approach to decrease the effects of smoking in pregnancy on newborn pulmonary function and respiratory morbidities. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00632476.

Cardiopulmonary and intracranial pressure changes related to endotracheal suctioning in preterm infants

Although endotracheal (ET) suctioning is performed frequently in sick newborn infants, its effects on cardiorespiratory variables and intracranial pressure (ICP) have not been thoroughly documented in neonates greater than 24 h who were not paralyzed while receiving mechanical ventilation. This study evaluates these changes in preterm infants who required ventilatory assistance. We measured transcutaneous PO2 and PCO2 (PtcO2 and PtcCO2, respectively), intra-arterial BP, heart rate, ICP, and cerebral perfusion pressure (CPP) before, during, and for at least 5 min after ET suctioning in 15 low birth weight infants less than 1500 g and less than or equal to 30 days of age. One infant was studied twice. A suction adaptor was used to avoid disconnecting the patient from the ventilator and to attempt to minimize hypoxemia and hypercapnia during suctioning. The patients were studied in the supine position and muscle relaxants were not used. PtcO2 decreased 12.1% while PtcCO2 increased 4.7% 1 min after suctioning; however, greater increases in mean BP (33%) and ICP (117%) were observed during suctioning. CPP also increased during the procedure. ICP returned to baseline almost immediately, whereas BP remained slightly elevated 1 min after suctioning. Our findings demonstrate that ET suctioning significantly increases BP, ICP, and CPP in preterm infants on assisted ventilation in the first month of life. These changes appear to be independent of changes observed in oxygenation and ventilation.

Survival, intracranial lesions, and neurodevelopmental outcome in infants with congenital diaphragmatic hernia treated with extracorporeal membrane oxygenation.

OBJECTIVE:Before the use of extracorporeal membrane oxygenation (ECMO), infants with a severe form of congenital diaphragmatic hernia (CDH) had a high mortality and morbidity. Recent studies have shown an improvement in the survival of these infants after ECMO treatment; however, the existing data do not provide sufficient information regarding the quality of survival and developmental outcome of these infants. The objective of this study was to evaluate survival, intracranial lesions, and the neurodevelopmental outcome of infants with CDH treated with ECMO.METHODS:We retrieved data for 51 (n = 51) infants with CDH who were treated with ECMO at Huntington Memorial Hospital between 1985 and 1994. Their mean gestational age was 38.5 ± 2.4 weeks (mean ± SD); their mean birth weight was 3170 ± 620 gm. Vital signs, arterial blood gases, chest radiographs, cranial and cardiac ultrasonography were routinely obtained before ECMO treatment. Cranial ultrasounds were performed daily on all infants while on ECMO; computerized tomography scans were obtained on all infants after completion of ECMO treatment. The surviving infants were followed at our neonatal follow-up clinic for neurodevelopmental assessment.RESULTS:A total of 39 infants were placed on venoarterial ECMO and 12 infants were placed on venovenous ECMO; a total of 35 infants had CDH repair before ECMO, whereas 16 infants had delayed surgery. A total of 31 infants (61%) survived. The infants who survived had a mean pH of 7.33 ± 0.20, mean airway pressure of 19.6 ± 5.8 cm H2O, and anoxygenation index (OI) of 87 ± 55 before ECMO intervention. The infants who expired (n = 20) had a mean pH of 7.31 ± 0.15, mean airway pressure of 23.1 ± 5.5 cm H2O, and a mean oxygenation index of 127 ± 56 before ECMO treatment. Before ECMO, survivors had a significantly lower oxygenation index and a higher PaO2 compared with nonsurvivors (p < 0.01). A total of 18 infants (35%) had abnormal central nervous system findings. Of the 51 infants, 10 had ventricular dilatation, 6 had intracranial hemorrhage, and 11 had focal or diffuse cerebral atrophy diagnosed by computerized tomography scan or at autopsy (1 patient had an infarct). Eight infants had more than one central nervous system abnormality. A total of 16 survivors had a neurodevelopmental evaluation at 12 months, and 11 of these survivors were evaluated at 24 months of age (Bayley Scales of Infant Development). The developmental progress of these infants falls within the low-average range of cognitive and motor abilities. Their mean Bayley Mental Developmental Index was 85 ± 25 (50 to 145) at 24 months; their Psychomotor Developmental Index was 89 ± 21 (50 to 113) at 24 months of age. Follow-up at 4 and 6 years of age is in progress.CONCLUSION: Our preliminary findings indicate that 35% of infants with severe CDH requiring ECMO had central nervous system abnormalities (intracranial lesions, including ventricular dilatation). The survival rate in our study population is consistent with recent reports. As a group, infants with severe CDH display mild neuromotor and cognitive delay in development at 24 months of age.

Effects of metaproterenol on pulmonary mechanics, oxygenation, and ventilation in infants with chronic lung disease

Changes in pulmonary resistance, dynamic compliance, tidal volume, and transcutaneous PO2 and PCO2 after nebulized administration of metaproterenol were evaluated in eight newborn infants (birth weight 650 to 1060 g, gestational age 25 to 28 weeks) with chronic lung disease receiving mechanical ventilation. The infants were monitored continuously before and for 15 minutes after nebulization of metaproterenol during 3 consecutive days at mean age 34 days. There were significant increases in compliance, tidal volume, and tcPO2, and significant decreases in pulmonary resistance and tcPCO2. These data show that bronchospasm contributes significantly to the high pulmonary resistance in preterm infants with chronic lung disease and that metaproterenol is beneficial in the therapy of infants with chronic lung disease requiring mechanical ventilation.

A comprehensive approach to the prevention of bronchopulmonary dysplasia

The current bronchopulmonary dysplasia (BPD) is seen in infants born extremely premature, with less severe respiratory distress syndrome (RDS) and who received prenatal steroids—“new BPD”. The pathophysiology of BPD is based on an impairment of lung maturation with prenatal and postnatal multi‐hit insults and genetic susceptibility. This multifactorial pathophysiology of BPD suggests that no single “magic bullet” will prevent it. Thus, to avoid BPD we need to implement a complex and comprehensive strategy.

Respiratory compliance in preterm infants after a single rescue course of antenatal steroids: a randomized controlled trial

OBJECTIVE To compare respiratory compliance and functional residual capacity in infants randomized to a rescue course of antenatal steroids vs placebo. STUDY DESIGN Randomized, double-blinded trial. Pregnant women > or =14 days after initial antenatal steroids were randomized to rescue antenatal steroids or placebo. The primary outcomes were measurements of respiratory compliance and functional residual capacity. This study is registered with clinicaltrials.gov (NCT00669383). RESULTS Forty-four mothers (56 infants) received rescue antenatal steroids and 41 mothers (57 infants) received placebo. There was no significant difference in birthweight, or head circumference. Infants in the rescue group had an increased respiratory compliance (1.21 vs 1.01 mL/cm H(2)O/kg; adjusted 95% confidence interval, 0.01-0.49; P = .0433) compared with placebo. 13% in the rescue vs 29% in the placebo group required > or =30% oxygen (P < .05). Patients delivered at < or =34 weeks had greater pulmonary benefits. CONCLUSION Infants randomized to rescue antenatal steroids have a significantly increased respiratory compliance compared with placebo.

Umbilical arteriovenous PO2 and PCO2 differences and neonatal morbidity in term infants with severe acidosis.

OBJECTIVE In term infants umbilical cord gas analysis is a poor predictor of immediate newborn complications associated with intrapartum asphyxia, unless the umbilical arterial pH is less than 7.00. We investigated whether umbilical arteriovenous blood gas differences may better predict asphyxia-related complications. STUDY DESIGN The study population consisted of 82 term, nonanomalous, singleton, live-born infants with severe umbilical acidosis (pH < 7.00). Umbilical arteriovenous pH, PCO2, and PO2 differences were correlated with Apgar scores and the presence of seizures, hypoxic-ischemic encephalopathy, cardiopulmonary and renal dysfunction, and abnormal development in the neonatal period. RESULTS Umbilical arteriovenous pH, PCO2, and PO2 differences were interrelated (p < 0.0001), but these parameters correlated only weakly with 1-minute and 5-minute Apgar scores. An arteriovenous PCO2 difference > 25 torr was a highly sensitive and specific parameter in identifying asphyxiated infants with seizures, hypoxic-ischemic encephalopathy, cardiopulmonary and renal dysfunction, and abnormal development in the neonatal period. Arteriovenous PO2 differences were less sensitive in the detection of neonatal morbidity than arteriovenous PCO2 differences. CONCLUSION Umbilical cord blood arteriovenous PCO2 differences provide a new tool to predict neonatal morbidity and permanent neurologic injury in term infants with perinatal asphyxia.

Venovenous versus venoarterial extracorporeal membrane oxygenation in congenital diaphragmatic hernia.

BACKGROUND Extracorporeal membrane oxygenation (ECMO) has a significant role as a final rescue modality in severe respiratory failure of the newborn with congenital diaphragmatic hernia (CDH). The objective of this study was to compare the efficiency of venovenous (VV) versus venoarterial (VA) ECMO in newborns with CDH. METHODS A retrospective report of 11 years experience (1990 through 2001) of a single center, comparing VV and VA ECMO is given. VV ECMO was the preferred rescue modality for respiratory failure unresponsive to maximal medical therapy. Only when the placement of a VV ECMO 14F catheter was not possible, VA ECMO was used. Forty-six patients met ECMO criteria; 26 were treated with VV ECMO and 19 with VA ECMO. One patient underwent conversion from VV to VA ECMO. RESULTS Before ECMO, there was no difference between VV and VA ECMO patients in mean oxygenation index (83 v 83), mean airway pressure (18.4 v 18.9 cm H(2)O), ECMO cannulation age (28 v 20 hours), or in the percentage of patients who needed dopamine and dobutamine (100% v 100%). From November 1994, nitric oxide (NO) was available; before ECMO, 11 of 14 (79%) VV ECMO patients received NO versus 9 of 10 (90%) patients in the VA group. VV ECMO patients were larger (3.34 v 2.77 kg; P <.05) and of advanced gestational age (39.0 v 36.9 wk; P <.05) compared with VA ECMO patients. There was no significant difference between VV and VA ECMO patients in survival rate (18 of 26, 69% v 13 of 19, 68%), ECMO duration (152 v 150 hours), time of extubation (32.0 v 33.5 days), age at discharge (73 v 81 days), or incidence of short-term intracranial complications (3.8% v 10.5%) or myocardial stun (3.8% v 15.8%). CONCLUSIONS The authors conclude that VV ECMO is as reliable as VA ECMO in newborns with CDH in severe respiratory failure who need ECMO support and who can accommodate the VV double-lumen catheter. Because of its potential advantages, VV ECMO may be the preferred ECMO method in these infants.

Regulation of pro-inflammatory cytokine expression by curcumin in hyaline membrane disease (HMD).

Persistent expression of pro-inflammatory cytokines is believed to play a major role in the pathogenesis of chronic lung disease (CLD) in premature infants. Inhibition of pro-inflammatory cytokine production in the lungs of preterm newborns may result in the attenuation of CLD. Curcumin is a naturally occurring phenolic compound derived from the food spice tumeric with broad based in vitro anti-inflammatory properties. In this study lung inflammatory cells from preterm newborns at risk for the development of CLD were derived via modified broncho-alveolar lavage and stimulated ex vivo with lipopolysaccharide (LPS) (10 ng/ml). Curcumin was added to these cultures at 0, 0.5 and 20 uM concentrations. Pro-inflammatory cytokine, TNFalpha, IL-1beta and IL-8 protein was measured from the culture supernatants 12 hours post culture. For control, adult peripheral blood mononuclear cells (PBMC) were cultured under the same conditions. Both neonatal lung inflammatory cells and adult PBMC produced high levels of pro-inflammatory cytokines in response to LPS. Curcumin produced significant inhibition of IL-1beta and IL-8 but minimal inhibition of TNFalpha expression by preterm lung inflammatory cells at 20 uM concentrations. Adult PBMC expression of IL-8 was significantly inhibited by curcumin at 20 uM concentrations. Therefore, curcumin inhibits pro-inflammatory cytokine production (TNFalpha, IL-1beta and IL-8) by lung inflammatory cells ex vivo. Pathways involved with curcumin regulation of these cytokines are developmentally intact and functional in premature infants. Curcumin may be effective as a therapeutic agent in the attenuation of CLD.