Neonatal intensive care applications of near-infrared spectroscopy.

Near-infrared spectroscopy (NIRS) is a noninvasive technique for assessing cerebral hemodynamic variables and oxidative status in the neonatal intensive care setting. It can be performed for extended periods of time at the bedside without interfering with routine patient care. NIRS appears to have the ability to not only assess relative changes in oxygenated and deoxygenated hemoglobin, total hemoglobin, and cytochrome aa3, but it can also produce estimates of cerebral blood volume and cerebral blood flow. Research data document significant changes in these hemodynamic variables with patient activity and clinical interventions in both premature and term infants. NIRS may evolve into an important diagnostic and prognostic tool for neonatal neurologic outcome.

A single very early dexamethasone dose improves respiratory and cardiovascular adaptation in preterm infants.

OBJECTIVES: To test the hypothesis that a single dose of dexamethasone given soon after delivery to infants <28 weeks' gestation leads to improved cardiopulmonary adaptation in the first week and lowers the risk of significant intraventricular hemorrhage. METHODS: In a prospective, blinded, placebo-controlled study, we randomly assigned 70 infants <28 weeks' gestation who were born in the hospital to receive dexamethasone (0.2 mg/kg) (n = 37) or normal saline solution (n = 33) within 2 hours of delivery. After an interim analysis showed that the incidence of intraventricular hemorrhage was much lower than expected, enrollment was stopped and we limited our analysis to a comparison of ventilator settings, blood pressure, and pressor use during the first 7 days. RESULTS: Clinical characteristics of the groups were comparable at study entry. Ventilator weaning occurred more rapidly in the patients who received dexamethasone: their intermittent mandatory ventilation rate was significantly lower on days 1 through 6, and their peak inspiratory pressure was lower on days 3 through 7 compared with the control group. Mean blood pressures were higher in the dexamethasone group within 12 hours and remained higher through day 5, but the use of pressors was not different. Fewer infants in the dexamethasone group received indomethacin to treat a patent ductus arteriosus (22% vs 47%, P <.03). CONCLUSION: Dexamethasone given within 2 hours of delivery to preterm infants <28 weeks' gestation resulted in lower ventilator settings and higher mean blood pressures during the first 7 days. Fewer infants required indomethacin to treat a patent ductus arteriosus.

Percutaneous central catheters and peripheral intravenous catheters have similar infection rates in very low birth weight infants.

OBJECTIVE: We performed this study to determine if percutaneous central lines (PCLs) were associated with infection more often than peripherally placed intravenous catheters (PIVs). STUDY DESIGN: We conducted a retrospective, cohort study of 53 infants with PCLs inserted from March 1993 to February 1995 for evidence of catheter-related bloodstream infection and 97 cohorts with PIVs who were matched to the infants with PCLs by admission date and birth weight. We considered an infant to have catheter-related bloodstream infection if bacteremia occurred while the PCL or PIV was in place with no other identifiable infection focus. Statistical analyses were performed by using either Student's t test or the Mann-Whitney U test where appropriate. RESULTS: There were eight infections per 1000 catheter days of PCL use and nine infections per 1000 catheter days of PIV use. CONCLUSION: PCLs do not become infected more often than PIVs.

Endotracheal continuous positive airway pressure after rescue surfactant therapy.

OBJECTIVE: To determine if premature infants greater than 31 weeks of gestation with established hyaline membrane disease (HMD) can be treated with endotracheal continuous positive airway pressure (ETCPAP) after rescue surfactant replacement therapy. STUDY DESIGN: Retrospective study of 46 premature infants (>31 weeks of gestation) admitted to Texas Children's Hospital with HMD. Tolerance to ETCPAP after surfactant replacement was evaluated. Prenatal and postnatal characteristics and outcome were compared in the success and failure groups. Multiple logistic regression was used to determine predictive factors associated with failure. RESULTS: Thirty infants (65.2%) were successfully treated with rescue surfactant and ETCPAP. Cesarean section, higher 1-minute Apgar score, and higher FiO2 level at entry were independent predictors of failure to remain on CPAP due to hypoxemia (56.3%), hypercapnia (31.2%), and apnea (12.5%). In the success group duration of intubation (p < 0.001), oxygen administration (p < 0.01), >40% oxygen requirement (p < 0.001), hospital stay (p < 0.05), and respiratory support on day 7 (p < 0.001) were significantly favorable. CONCLUSION: Two thirds of infants greater than 31 weeks of gestation, with HMD needing rescue surfactant treatment, can be successfully managed with ETCPAP.

Long-term neurodevelopmental outcome after intrauterine transfusion for the treatment of fetal hemolytic disease.

OBJECTIVE: The aim of the study was to assess the developmental outcome of neonatal survivors of hemolytic disease of the neonate treated with modern intrauterine transfusion techniques. STUDY DESIGN: In this prospective, observational study, auditory evoked-response tests were performed in the nursery. Neurodevelopmental evaluation with the Gesell Developmental Schedules was performed between 9 and 18 months of corrected age to assess motor skills, language development, comprehension capacity, and social skills. The McCarthy Scales of Children's Abilities were administered between 36 and 62 months. RESULTS: Forty children who survived severe fetal hemolytic disease were followed up until 62 months old. Demographic data included gestational age at first intrauterine transfusion (26.4 +/- 3.7 weeks), median number of intrauterine transfusions (4, range 1-8), lowest fetal hematocrit (20.2% +/- 7.8%), peak fetal bilirubin (7.1 +/- 2.1 mg/dL), incidence of hydrops fetalis (45%), and mean gestational age at delivery (35.6 +/- 2.2 weeks). One case of severe bilateral deafness and 1 case of right spastic hemiplegia were diagnosed. The Gesell Developmental Schedules score was assessed between 9 and 18 months of corrected age in 22 infants. The global developmental quotient was 101.9 +/- 9.5 (mean for normal population is 100). Regression analysis revealed no correlation between the global developmental quotient and gestational age at the first intrauterine transfusion, gestational age at birth, or the severity of the fetal hemolytic disease (fetal hematocrit, fetal bilirubin, presence of hydrops fetalis, total number of intrauterine transfusions, duration of neonatal phototherapy, and number of neonatal exchange transfusions). Eleven of the 40 children were followed up until they were 62 months old, and the McCarthy Scales of Children's Abilities were administered. The mean cognitive index was 107.6 +/- 9.4 (90-109 is considered average). CONCLUSION: Despite severe fetal hemolytic disease, normal developmental outcome can be expected for children treated with intrauterine transfusions.

Treatment of obstructive jaundice in erythroblastosis fetalis with ursodeoxycholic acid (UDCA): a case report.

OBJECTIVE: To report a significant improvement of direct hyperbilirubinemia values, in an infant with cholestasis secondary to erythroblastosis fetalis, after treatment with ursodeoxycholic acid (UDCA). STUDY DESIGN: Case report. RESULTS: A full term infant, with total and direct bilirubin values of 26 mg/dl (445 micromol/l) and 24.5 mg/dl (419 micromol/l), respectively, on the third day of life, had total and direct bilirubin values of 8.2 mg/dl (140 micromol/l) and 6.9 mg/dl (118 micromol/l), respectively, after 2 days of treatment with UDCA. Because the natural course of this cholestasis takes several weeks to resolve, the observed improvement is highly suggestive of a direct effect of UDCA on the disease course. CONCLUSION: This treatment may add a new therapeutic option to the limited measures available for this condition, although further studies regarding safety and its mechanism of action are needed before it can be routinely recommended.

Does extracorporeal membrane oxygenation benefit neonates with congenital diaphragmatic hernia? Application of a predictive equation.

The overall survival of neonates with congenital diaphragmatic hernia (CDH) remains poor despite the advent of extracorporeal membrane oxygenation (ECMO). Attempts at accurately predicting survival have been largely unsuccessful. The purpose of this study was twofold: (1) to identify independent predictors of survival from a cohort of CDH neonates treated at the authors' institution when ECMO was not available and combine them to form a predictive equation, and (2) to apply the equation prospectively in a cohort of CDH neonates, treated at the same institution when ECMO was available, to determine whether ECMO improves outcome. From the clinical data of 62 CDH neonates treated at the authors' center by the same team of university neonatologists and pediatric surgeons between 1983 and 1993 (before ECMO availability), 15 preoperative and seven operative variables were selected as potential independent predictors. When subjected to multivariate, stepwise logistic regression analysis, four variables were identified as statistically significant (P < .05), independent predictors of survival: (1) ventilatory index (VI), (2) best preoperative PaCO2, (3) birth weight (BW), and (4) Apgar score at 5 minutes. When combined via logistic regression analysis, the following predictive equation was formulated: P (probability of survival to discharge) = [1 + e(x)]-1 where x = 4.9 - 0.68 (Apgar) - 0.0032 (BW) + 0.0063 (VI) + 0.063 (PaCO2). Applying a standard cut-off rate of survival at less than 20%, the equation yielded a sensitivity of 94% and a specificity of 82% in identifying the correct outcome of patients treated with conventional ventilatory management. The overall survival rate was 66%. Since the availability of ECMO at the center, 32 CDH neonates were treated using the same conventional ventilatory treatment and surgical repair by the same university staff. The overall survival rate was 69%. The predictive equation was applied prospectively to all neonates to determine predicted outcome, but was not used to decide the treatment method. Eighteen neonates received conventional therapy alone; 16 of 18 survived (89%). Fifteen of the 16 patients who survived had their outcomes predicted correctly (94%). Fourteen neonates did not respond to conventional therapy and required ECMO; 6 of 14 survived (43%). Six of the eight patients predicted to survive, lived (75%). All six patients predicted to die, died despite the addition of ECMO therapy (100%). The mean hospital cost, per ECMO patient who died, was $277,264.75 +/- $59,500.71 (SE). An odds ratio analysis, using the four independent predictors to standardize for degree of illness, was performed to assess the risk associated with adding ECMO therapy. The result was 1.25 (P = 0.75). Although the cohort was not large enough to eliminate significant beta error, the data strongly suggested no advantage of ECMO. At this center, absolute survival rates for neonates with CDH have not been significantly altered since ECMO has become available (66% v 69%). The authors conclude that the predictive equation remains an accurate measurement of survival at their center even when ECMO is used as a salvage therapy. The method of creating a predictive equation may be applied at any institution to determine the potential outcome of CDH neonates and assess the effect of ECMO, or other salvage therapies, on survival rates.

Antenatal steroids are associated with less need for blood pressure support in extremely premature infants.

OBJECTIVE: To determine if antenatal steroids decrease the amount of blood pressure support required by extremely premature infants between 23 and 27 weeks' gestation. DESIGN: Retrospective cohort study. SETTING: Texas Children's Hospital neonatal intensive care unit from January 1986 to December 1991. PARTICIPANTS: Two hundred forty premature infants between 23 and 27 weeks' gestation who survived at least 48 hours. MAIN OUTCOME MEASURES: The amount of blood pressure support received in the form of dopamine and colloid. Secondary analysis investigated differences in mortality, respiratory support requirements, the incidence of intraventricular hemorrhage, necrotizing enterocolitis, infection, retinopathy of prematurity requiring surgery, and the length of hospitalization. RESULTS: During the first 48 hours of life, premature newborns exposed to antenatal corticosteroids were less likely to receive dopamine for blood pressure support (47% vs 67%), and if they did, the amount of dopamine expressed as a dopamine score was less than that received by those infants not exposed to antenatal corticosteroids (281 +/- 240 vs 407 +/- 281). Those exposed to antenatal corticosteroids also had a lower mortality rate (8% vs 24%) and lower respiratory support requirements. The incidence of grade 3 or 4 intraventricular hemorrhage was 8% in infants exposed to antenatal corticosteroids and 17% in infants not exposed. No difference was found in the incidence of necrotizing enterocolitis, infection, or retinopathy of prematurity requiring surgery, or length of hospitalization. CONCLUSION: Receipt of antenatal corticosteroids is associated with less need for blood pressure support during the first 48 hours after birth in premature infants between 23 and 27 weeks' gestation.

Factors associated with umbilical catheter-related sepsis in neonates.

To determine factors associated with risk for umbilical catheter-related sepsis, we studied neonates with one or more catheters in place for more than 3 days. Among 225 infants with 357 umbilical catheters, catheter-related sepsis occurred in 14 infants (6%). Catheter-related sepsis occurred in 5% of infants with umbilical arterial catheters and in 3% of infants with umbilical venous catheters. Staphylococcal species accounted for 71% of cases of catheter-related sepsis. Multiple logistic regression analysis revealed that very low birth weight and longer duration of antibiotic therapy were significantly associated with risk for umbilical arterial catheter-related sepsis. Increased risk for umbilical venous catheter-related sepsis was best predicted by the simultaneous occurrence of higher birth weight and infusion of hyperalimentation solution. Catheter duration correlated with duration of antibiotic therapy and with infusion of hyperalimentation solution for both types of catheters; however, in the multivariable analysis, duration of catheterization was not found to be a significant independent predictor of risk for catheter-related sepsis for either type of catheter.

Reduction in plasma protein does not affect body water content in fetal sheep.

We performed this study to determine if isolated hypoproteinemia and low colloid osmotic pressure cause formation of fetal edema. We successfully operated on six sets of twin fetal sheep at 114 d gestation to insert catheters into arteries and veins of both fetuses, allowing us to chronically perform partial exchange transfusions. One twin underwent protein reduction by repeated partial exchange transfusion over 3 d, and the other twin underwent simultaneous sham procedures. We removed an average of 18 g of protein, causing a 41% decrease in plasma protein concentration and a 44% decrease in colloid osmotic pressure. Vascular pressures, heart rate, hematocrit, plasma osmolarity, arterial pH, and arterial PO2 were not affected by protein reduction or by sham procedure, whereas PCO2 increased by a small amount in both groups. At autopsy, none of the fetuses in either group were edematous. Measurements of total body water by the wet to dry method, chloride space, and amniotic and allantoic fluid volumes were similar in both groups. We conclude that hypoproteinemia of a short duration does not affect the body water content of fetal sheep.

Reversal of venous blood flow with atrial tachycardia and hydrops in fetal sheep.

The purpose of this project was to characterize the reversal of blood flow in the proximal inferior vena cava (IVC) seen in fetal sheep with pacing-induced atrial tachycardia and hydrops. We successfully operated on seven pregnant ewes at 118-130 d gestation to attach ECG and pacing wires, insert vascular catheters, and place Doppler flow probes around the common aortic trunk and the IVC. We also performed two-dimensional and Doppler ultrasonographic exams at baseline, after initiation of pacing, and daily thereafter. All fetuses developed hydrops. Ultrasonographic appearance of ascites and pleural effusion occurred within 4 h in four fetuses and within 48 h in all fetuses. Atrial pacing did not affect arterial pH or arterial O2 tension, but arterial CO2 tension increased by a small amount. Mean IVC pressure increased 75%, whereas mean aortic pressure remained the same. Concentrations of plasma protein and albumin and the hematocrit did not change with atrial pacing. Doppler ultrasound examination and Doppler IVC flow tracings showed that flow reversal began immediately with atrial pacing and disappeared immediately with cessation of pacing. Reversed flow was 21% of forward flow. Inspection of simultaneous recordings of ECG, Doppler aortic and IVC flows, and aortic and IVC pressure tracings revealed that the reversed blood flow occurred in diastole in conjunction with atrial contraction and, therefore, could not be due to tricuspid insufficiency. Our findings of increased venous pressure and reversed venous blood flow suggest that ventricular function is impaired and further suggest that oxygen supply to the ventricles may not be sufficient for the increased demand.

Barotrauma and microvascular injury in lungs of nonadult rabbits: effect of ventilation pattern.

To study the pulmonary microvascular injury produced by ventilation barotrauma, the isolated perfused lungs of 4 to 6-wk-old New Zealand white rabbits were ventilated by one of the following methods: peak inspiratory pressure (PIP) 23 cm H2O, gas flow rate 1.1 L/min (group 1); PIP 27 cm H2O, gas flow rate 6.9 L/min (group 2); PIP 50 cm H2O, gas flow rate 1.9 L/min (group 3); or PIP 53 cm H2O, gas flow rate 8.3 L/min (group 4). Microvascular permeability was assessed using the capillary filtration coefficient (Kfc) before and 5, 30, and 60 min after a 15-min period of ventilation. Baseline Kfc was not significantly different between groups. A significant increase over the baseline Kfc was noted at 60 min in group 2 and in all postventilation Kfc values in groups 3 and 4 (p less than .05). Group 1 Kfc values did not change significantly after ventilation. At all post-ventilation times, values for Kfc were significantly greater in groups 3 and 4 than in group 1 (p less than .05). Group 4 Kfc values were significantly greater than those in group 2 at 5 and 30 min postventilation. These data indicate that high PIP, and to a lesser extent, high gas flow rates cause microvascular injury in the compliant nonadult lung and suggest that the combination of high PIP and high gas flow rates are the most threatening to microvascular integrity.

Atrial tachycardia causes hydrops in fetal lambs.

The purpose of this project was to study mechanisms responsible for edema formation in fetuses with hydrops. We produced hydrops fetalis in 28 fetal sheep [gestational age of 125 +/- 5 days (mean +/- SD)] by pacing their atria at 300-320 beats/min for 68 +/- 40 (SD) h. All fetuses developed peripheral edema and ascites [volume of ascitic fluid was 134 +/- 75 (SD) ml; total protein concentration was 3.10 +/- 0.6 (SD) g/dl, and total albumin concentration was 1.68 +/- 0.3 (SD) g/dl]. Pacing did not affect aortic pressure but increased venous pressure from 4 +/- 1 to 8 +/- 1 (SE) Torr. Pacing did not affect pH, arterial partial pressure of O2 (PaO2), or Na+ but increased PaCO2 from 53 +/- 1 to 55 +/- 1 (SE) Torr and K+ from 3.9 +/- 0.1 to 4.3 +/- 0.1 (SE) meq/l. Hematocrit increased from 29 +/- 1 to 32 +/- 1 (SE)% acutely with pacing but returned to base line by the last day of the experiment. Plasma protein concentration decreased slightly from 3.7 +/- 0.1 to 3.5 +/- 0.1 (SE) g/dl by the last day of the experiment; plasma albumin concentration did not change. Plasma volume decreased acutely from 271 +/- 19 to 238 +/- 16 (SE) ml and then remained decreased throughout the experiment. Red blood cell mass and the turnover time for albumin were not affected by pacing. We found no consistent relationship between edema formation and changes in arterial blood gas tensions, plasma protein concentrations, or the turnover time for albumin.2

Chest wall restriction limits high airway pressure-induced lung injury in young rabbits.

High peak inspiratory pressures (PIP) during mechanical ventilation can induce lung injury. In the present study we compare the respective roles of high tidal volume with high PIP in intact immature rabbits to determine whether the increase in capillary permeability is the result of overdistension of the lung or direct pressure effects. New Zealand White rabbits were assigned to one of three protocols, which produced different degrees of inspiratory volume limitation: intact closed-chest animals (CC), closed-chest animals with a full-body plaster cast (C), and isolated excised lungs (IL). The intact animals were ventilated at 15, 30, or 45 cmH2O PIP for 1 h, and the lungs of the CC and C groups were placed in an isolated lung perfusion system. Microvascular permeability was evaluated using the capillary filtration coefficient (Kfc). Base-line Kfc for isolated lungs before ventilation was 0.33 +/- 0.31 ml.min-1.cmH2O-1.100g-1 and was not different from the Kfc in the CC group ventilated with 15 cmH2O PIP. Kfc increased by 850% after ventilation with only 15 cmH2O PIP in the unrestricted IL group, and in the CC group Kfc increased by 31% after 30 cmH2O PIP and 430% after 45 cmH2O PIP. Inspiratory volume limitation by the plaster cast in the C group prevented any significant increase in Kfc at the PIP values used. These data indicate that volume distension of the lung rather than high PIP per se produces microvascular damage in the immature rabbit lung.

Effects of arginine vasopressin on hemodynamics and lung fluid balance in lambs.

The purpose of this project was to study the effects of increased plasma concentrations of arginine vasopressin (AVP) on hemodynamics and lung fluid balance in lambs. We studied 16 unanesthetized newborn lambs during a base-line period and while infusing AVP into a hindlimb vein at 1.65 +/- 0.12 and 2.98 +/- 0.15 mU.kg-1.min-1. We measured aortic, pulmonary arterial, and left atrial pressures and heart rate continuously and cardiac output at frequent intervals. In five additional experiments, we collected samples of pure lung lymph during a base-line period and while infusing AVP at 2.02 +/- 0.15 mU.kg-1.min-1. AVP infusion increased plasma concentrations of AVP to 11.3 +/- 5.2 and 19.9 +/- 5.2 microU/ml at the low and high rates of infusion, respectively. Both aortic and left atrial pressures increased at the low rate of infusion (11 and 3 Torr, respectively) but remained unchanged at the higher rate. Systemic vascular resistance increased, and heart rate and cardiac output decreased at each rate of infusion. In fact, at the higher rate of infusion cardiac output decreased 38% when compared with base line. Neither pulmonary artery pressure nor pulmonary vascular resistance was affected by infusion of AVP. Despite the increase in left atrial pressure, the rate of lung lymph flow was not affected by the infusion of AVP, whereas the lymph-to-plasma protein ratio decreased slightly but significantly from 0.64 +/- 0.02 to 0.60 +/- 0.02.(ABSTRACT TRUNCATED AT 250 WORDS)