Effects of cisapride on QTc interval in neonates

AIM—Prospective survey of the effects of cisapride on QTc interval in neonates given cisapride.METHODS—QTc interval was determined just before and 2.9 (0.9) days after outset of the treatment in 49 neonates treated with cisapride between 1 August 1995 and 29 February 1996.RESULTS—Cisapride significantly increased QTc interval (p = 0.0001), and this was higher when birthweight or gestational age were lower. The prolongation of QTc interval above the arbitrary value of 0.450 (n = 7) was clinically asymptomatic and was significantly more common in the infants born with a gestational age ? 33 weeks (n = 6).CONCLUSION—The findings indicate that cisapride accumulates in less mature neonates. Further pharmacokinetic studies are needed.     

High frequency oscillatory ventilation in infants with increased intra-abdominal pressure

AIMS—To describe the short term effect of high frequency oscillatory ventilation on infants with severe abdominal distension who could not be conventionally ventilated.METHODS—Eight infants (25 to 38 gestational weeks, birthweight 600-3200 g, postnatal age 1 to 190 days) with a variety of intra-abdominal pathologies, resulting in severe abdominal distension and failure of conventional ventilation, were studied.RESULTS—The oxygenation status of all infants significantly improved within an hour of changing from conventional to high frequency oscillatory ventilation. Infants who were hypercapneic on conventional ventilation also showed a reduction in PaCO₂. As a group, the mean (SD) PaO₂/FIO₂ improved from 4.99 (0.98) kpa to 11.55 (3.8) kpa (P = 0.002), and the PaCO₂ from 6.48 (2.12) kpa to 4.89 (1.22) kpa (P= 0.028). These improvements were sustained throughout the next 48 hours.CONCLUSION—High frequency oscillatory ventilation seems to be an effective rescue measure for infants with respiratory failure secondary to increased intra-abdominal pressure.     

Effect of cisapride on gastric emptying in premature infants with feed intolerance

OBJECTIVE: To assess the effect of cisapride on gastric emptying and gastro-oesophageal reflux (GOR) symptoms in preterm infants with feed intolerance. METHODS: Sixteen preterm infants (gestational age 24-35 weeks) with feed intolerance were enrolled in the study. Infants were randomized to receive 7 days of cisapride 0.2 mg/kg four times a day, immediately followed by 7 days of placebo or vice versa. Gastric emptying was measured using the [13C]-octanoic acid breath test prior to study entry and repeated on day 5, 6 or 7 after randomization and 5, 6 or 7 days after crossover. The symptoms of GOR were monitored during the study period using a standardized reflux chart. Weight was recorded daily. RESULTS: There was no change in gastric emptying in infants prescribed cisapride (gastric half-emptying time (t1/2) 31.9 +/- 4.7 vs 34.2 +/- 3.9 min for placebo vs cisapride, respectively; P = 0.65). Infants on cisapride had slower growth and there was no change in reflux symptoms. CONCLUSIONS: The use of cisapride in preterm infants with feed intolerance cannot be recommended.     

Assessment of spontaneous baroreflex sensitivity in neonates

AIMS—To determine whether it is possible to assess baroreflex sensitivity in neonates by studying only spontaneous variations in systolic blood pressure and heart rate.METHODS—ECG and non-invasive blood pressure signals were continuously studied in 14 preterm neonates (term 29-32 weeks) and five term neonates (term 40-41 weeks). Non-invasive blood pressure measures were obtained using a Finapres placed around the child''s wrist. Both signals (ECG and blood pressure), sampled at 400 Hz, were digitised by an A/D converter and stored in a binary mode on magnetic disk. An inhouse software QRS detection algorithm was used to define R peaks of the QRS complexes with an accuracy greater than 2 ms. Four 4 minute periods were recorded in each infant. The slope of the linear regression of RR intervals versus systolic blood pressure was calculated in each period and the mean value of the four slopes was then considered as the index of baroreflex sensitivity (in ms/mm Hg) in each neonate.RESULTS—Spontaneous baroreflex sensitivity was lower in preterm neonates than in term neonates (mean(SD): 4.07 (2.19) ms/mm Hg vs 10.23 (2.92) ms/mm Hg).CONCLUSION—Baroreflex sensitivity can be assessed in term and preterm neonates by studying spontaneous variations in systolic blood pressure alone. This method could be useful for studying the ontogeny of baroreflex sensitivity and might therefore provide information about the maturation of the autonomic nervous system.     

A double-blind placebo-controlled study on prophylactic use of cisapride on feed intolerance and gastric emptying in preterm neonates

OBJECTIVE: To evaluate whether prophylactic use of cisapride will reduce the incidence of feed intolerance and gastro-esophageal reflux, and improve gastric emptying in early neonatal period in preterm babies. DESIGN: Double blind randomized controlled trial. SETTING: Hospital based. SUBJECTS: Forty nine preterm babies between 29-34 weeks of gestation were administered either cisapride or placebo. METHODS: Babies were enrolled in the study once they reached 30 ml/kg/day of enteral feeding or when 25% of total fluid intake was received through the enteral route. Those with sepsis, congenital malformations and on aminophylline were excluded. The subjects were randomized to receive either cisapride or placebo in a dose of 0.2 mg/kg/dose every 8 hourly for 14 days or till discharge. During the study period babies were observed for clinical signs of feed intolerance as judged by increase in abdominal girth, increased prefeed gastric residuals or vomiting. Gastro-esophageal reflux and gastric emptying time was assessed by Technetium phytate scan on day 7 +/- 1. RESULTS: Feed intolerance was noticed in 59% of study and 41% of control population. No significant difference was noticed in the two groups in the total number of episodes of feed intolerance (1.54 +/- 2.4 vs 1.18 +/- 1.6). Nearly 50% of babies in each group had gastro-esophageal reflux. Gastric emptying time (mean (SD) and median) was found to be comparable (p = 0.70) in those on drug and placebo (58.1 (32.2 min) 48.8 min) vs (53.8 (34.6 min) 43.4 min). CONCLUSION: Cisapride does not reduce the incidence of feed intolerance, gastro-esophageal reflux and does not improve gastric emptying in normal preterm neonates.     

Randomised controlled trial of cisapride in feed intolerance in preterm infants

AIM—To assess the efficacy of cisapride in reducing the time required to establish enteral feeds in preterm infants.
METHODS—A randomised, double blind, placebo controlled trial was conducted of 34 infants of ⩽ 32 weeks of gestation, assigned to receive either cisapride 0.2 mg/kg/dose four times daily (n=18) or placebo (n=16).
RESULTS—The time taken by the babies to tolerate full enteral feeds was not significantly different between the groups (median 9.5days vs 10 days). There was a significantly lower incidence of large gastric residuals and regurgitation in the treated group compared with the placebo group. The number of episodes of large gastric residuals per infant was also significantly less. No adverse effects were noted.
CONCLUSION—The routine use of cisapride in preterm infants cannot be recommended to decrease the time to establish enteral feeds. Its use may be justified for clincally significant gastric stasis or regurgitation.

     

Treatment of patent ductus arteriosus with ibuprofen

AIM—To evaluate the efficiency and side effects of ibuprofen for the early treatment of patent ductus arteriosus (PDA)and compare it with indomethacin.METHODS—Forty preterm infants with gestational ages of less than 33 weeks, with respiratory distress syndrome (RDS) and echocardiographically confirmed PDA, were randomly assigned at days 2 to 3 of life to receive either intravenous indomethacin 3 × 0.2 mg/kg at 12 hour intervals or intravenous ibuprofen 1 × 10 mg/kg, followed by 5 mg/kg 24 and 48 hours later.RESULTS—PDA closed in 15 of 20 patients from the indomethacin group (75%) and in 16 of 20 (80%) from the ibuprofen group. Seven patients (three indomethacin, four ibuprofen) required a second treatment with indomethacin and in five (three in the indomethacin group and two in the ibuprofen group) the duct was ultimately ligated. Ibuprofen patients had a better urinary output and showed no increase in serum creatinine concentrations compared with the indomethacin group. Ibuprofen was not associated with any other side effect.CONCLUSIONS—Ibuprofen treatment seems to be as efficient as indomethacin in closing PDA on the third day of life in preterm infants with respiratory distress syndrome and seems to have fewer renal side effects.     

Outcome of fetuses with heart disease diagnosed in utero

OBJECTIVE—To review the outcomes of 193 fetuses with cardiac abnormalities detected by echocardiography.METHODS—A total of 422 fetuses between 16 and 41 gestational weeks, referred to paediatric cardiologists for detailed echocardiography, were included in this study.RESULTS—Structural heart defects were found in 55 (28%), isolated arrhythmia in 105 (54%), and other non-structural abnormalities (dilated cardiomyopathy, hypertrophic cardiomyopathy, aneurysm of the foramen ovale, isolated pericardial effusion or echogenic foci) in 33 (17%) of 193 fetuses. Total mortality was 26%. The prognosis was poor in fetuses with structural heart defects; 37 of 55 cases (67%) died in utero or postnatally. Chromosomal abnormality was associated with structural heart defect in 38% of fetuses, of whom 38% died. Among fetuses with isolated arrhythmia survival was 95%. Poor outcome was associated with complete heart block (n=14) in 2 (14%) fetuses with hydrops and heart rate of less than 55 per minute, and with supraventricular tachycardia (n=21) in three (14%) neonates delivered prematurely at a mean gestational age of 33 weeks. Furthermore, nine of 12 fetuses (75%) with structural heart defects and arrhythmia died. Among fetuses with non-structural cardiac abnormalities, survival was 73%. Poor outcome was evident in fetuses with dilated cardiomyopathy in eight of 13 (62%) and with hypertrophic cardiomyopathy in one of eight (13%) of cases.CONCLUSIONS—Factors associated with a poor prognosis were: structural heart defect associated with chromosomal abnormality or arrhythmia, congestive heart failure associated with supraventricular tachycardia or complete heart block, especially if delivery occurs preterm; and fetal hydrops with congestive heart failure and atrioventricular valve regurgitation.     

Cardiac effects of short course dexamethasone in preterm infants

AIM—To examine the incidence and natural history of left ventricular hypertrophy (LVH) associated with the shorter 2-3 week course of dexamethasone, now more usual, for chronic lung disease.METHOD—Thirty one infants, gestational age 23-34 (median 26) weeks, birthweight 500-2054 (median 815)g, received dexamethasone, starting at 0.4-0.6 mg/kg/day, at a median of 11 days of age (range 2-34), weaning over a period of 2-3 weeks. Eighteen preterm neonates were studied as controls over a similar time period. Serial echocardiographic measurements of end diastolic interventricular septum (IVSd) and left ventricular posterior wall (LVPWd) thicknesses were taken before, and up to 48 days after, starting dexamethasone. Maximum Doppler blood flow velocities from the left ventricular outflow tract (LVOT) were measured.RESULTS—Left ventricular hypertrophy (LVH) occurred in 29 babies (94%). Median hypertrophy of the IVSd in those receiving dexamethasone was 67% and LVPWd 56% of baseline measurements, significantly greater than control infants (p<0.001). LVH appeared by a median of three days, peaking by a median of 10 days. All resolved by a median of 27 days. LVOT obstruction was not seen. There was no significant correlation with birthweight, gestation, blood pressure, or glucose tolerance.CONCLUSIONS—LVH developed in almost all preterm neonates receiving a 2-3 week course of dexamethasone, but was of little clinical importance and always resolved. Echocardiography is probably not required routinely in infants receiving such short course dexamethasone for chronic lung disease.     

Oral Ibuprofen and Ductus Arteriosus Closure in Full-Term Neonates: A Prospective Case–Control Study

Management of patent ductus arteriosus (PDA) in full-term neonates remains controversial. We evaluated the effects of oral ibuprofen on PDA closure in 51 full-term neonates. All neonates were >3-days-old and had a gestational age ≥37 weeks. Patients with ductal-dependent congenital heart disease or severe pulmonary artery hypertension (gradient >40 mmHg) were excluded. Patients were randomly assigned to the treatment group (n = 30) or the control group (n = 21). The treated group received ibuprofen suspension (initially 10 mg/kg, then two 5-mg/kg doses 24 h apart), and control neonates received a placebo. Physicians who treated the patients were blinded to group assignment. There was a statistically significant difference in the closure rate of PDA between the treated (73.3%) and control groups (42.9%, P = 0.029). Among neonates with PDA closure, there was a significant difference in the day of closure between the two groups (25.49 and 17.65% on the days 4 and 14 after diagnosis of PDA in treated neonates versus 1.96 and 15.69% in controls, respectively). This study showed the efficacy of oral ibuprofen in achieving earlier closure of PDA in full-term neonates.     

Slow versus rapid enteral feeding advancement in preterm newborn infants 1000–1499 g: a randomized controlled trial

Aim:  To evaluate whether preterm neonates weighing 1000–1499 g at birth receiving rapid enteral feeding advancement at 30 mL/kg/day attain full feedings (180 mL/kg/day) earlier than those receiving slow enteral feeding advancement at 20 mL/kg/day without increase in the incidence of feeding intolerance or necrotizing enterocolitis.
Methods:  A total of 100 stable intramural neonates weighing between 1000 and 1499 g and gestational age less than 34 weeks were randomly allocated to enteral feeding (expressed human milk or formula) advancement of 20 mL/kg/day (n   = 50) or 30 mL/kg/day (n   = 50).
Results:  Neonates in the rapid feeding advancement group achieved full volume feedings before the slow advancement group (median 7 days vs. 9 days) (p < 0.001), had significantly fewer days of intravenous fluids (median 2 days vs. 3.4 days) (p < 0.001), shorter length of stay in hospital (median 9.5 days vs. 11 days) (p = 0.003) and regained birth weight earlier (median 16 days vs. 22 days) (p < 0.001). There were no statistical differences in the proportion of infants with apnea, feed interruption or feed intolerance.
Conclusion:  Rapid enteral feeding advancements of 30 mL/kg/day are well tolerated by stable preterm neonates weighing 1000–1499 g.     

Diagnosis of late onset neonatal sepsis with cytokines,adhesion molecule,and C-reactive protein in preterm very low birthweight infants

AIMS—To evaluate the commonly used markers—namely IL-6, TNFα, IL-1β, C-reactive protein and E-selectin for identification of late onset neonatal sepsis; to define the optimal cutoff value for each marker in preterm neonates; to assess whether these markers could assist in early discontinuation of antibiotics in non-infected cases; and to delineate the profile of these markers during systemic infection and in relation to successful treatment.METHODS—Very low birthweight infants in whom clinical sepsis was suspected when they were >72 hours of age were eligible for study. A full sepsis screen was performed in each episode. Cytokines, C-reactive protein, and E-selectin were serially measured on days 0 (at the time of sepsis evaluation), 1, 2, 4 and 7. The optimal cutoff value for each marker was calculated after minimising the number of misclassified episodes over all possible cutoff values for days 0 and 1. The sensitivity, specificity, positive and negative predictive values for each test and combination of tests for predicting systemic infection were also determined.RESULTS—One hundred and one episodes of suspected clinical sepsis were investigated in 68 infants. Forty five episodes were proved to be infections. The optimal cutoff values were IL-6 31 pg/ml, TNFα 17 pg/ml, IL-1β 1 pg/ml, C reactive protein 12 mg/l and E-selectin 174 ng/ml. IL-6 had the highest sensitivity (89%) and negative predictive value (91%) for detecting late onset infection on day 0. However, between 24 and 48 hours of onset, C-reactive protein was the best single marker, with an overall sensitivity and specificity of 84% and 96%, respectively. The use of serial and multiple markers in the first 48 hours further enhanced the sensitivity and specificity of these tests. Performing IL-6 and C-reactive protein on day 0, together with either TNFα on day 1 or C-reactive protein on day 2, showed the best overall sensitivity (98%) and specificity (91%) for the diagnosis of late onset infection.CONCLUSIONS—Optimal cutoff values for these markers in detecting late onset systemic infection in very low birthweight infants have been defined. Withholding antibiotic treatment at the onset of infection could be fatal and is not recommended, but the concomitant use of IL-6 and C-reactive protein or TNFα should allow antimicrobial treatment to be discontinued at 48 hours without waiting for microbiological results, provided that the infants are in good clinical condition.     

Effects of cisapride on QTc interval in term neonates

BACKGROUND: Cisapride administration for 48 hours has been shown to increase heart rate corrected QT (QTc) interval in preterm neonates. Accumulation of the drug because of liver enzyme immaturity has been suggested to be the reason. If this is correct, a longer survey of QTc interval should disclose an increase even in term neonates. OBJECTIVE: A prospective survey of the effects of cisapride on QTc interval in term neonates administered cisapride. SETTING: Neonatal Unit of the University Hospital of Dijon, France. DESIGN: QTc interval was determined just before and 48 hours, seven days, and 15 days after the start of treatment. SUBJECTS: Twenty one term newborn infants (mean gestational age 39.3 weeks) given the recommended dose of cisapride (0.2 mg/kg, four times a day). RESULTS: Administration of cisapride caused a significant increase in QTc interval (p < 0. 01). The mean value increased from 0.397 before treatment to 0.418 after 48 hours, 0.431 by day 7, and 0.447 by day 15. A QTc interval exceeding 0.450 was found in six neonates: three at 48 hours, one at day 7, and two at day 15. In two infants, withdrawal of the drug was associated with normalisation of the QTc interval. CONCLUSIONS: These results support the hypothesis of cisapride accumulation in newborns due to enzymatic immaturity and indicate that QTc interval should be monitored in neonates receiving this drug.     

Capillary refilling time in newborn babies: normal values

AIM—To assess the normal values of capillary refilling time (CRT) in healthy newborn babies; to assess the effect of different nursery containers (incubator, radiant warmer, crib), phototherapy, birthweight, gestational age, size for gestational age and sex on CRT; to compare CRT at different body sites as well as to assess the variation between observers.METHODS—Healthy neonates (n = 469) of different gestational ages and different sizes for gestational age, were studied 1 to 7 days after birth. CRT was measured in four of the most suitable sites—namely, midpoints of the sternum and the forehead, the palm of the hand and the plantar surface of the heel (defined as chest, head, palm and heel, respectively). The applied pressing time was 5 seconds. CRT was measured with a manual stopwatch.RESULTS—Only the chest and the head distribution curves followed the Gaussian curve. The mean values and standard deviation of CRT in all tested nursery containers, including phototherapy for the chest, ranged from 1.82 (0.34) seconds to 2.01 (0.423) seconds, and for the head from 1.59 (0.36) seconds to 1.83 (0.31) seconds. The mean value of chest CRT was always longer than the head CRT for all parameters. Significant differences were found between different nursery containers, receivers, and non-receivers of phototherapy and between observers. No difference was found between sex, birthweight, gestational age and size for gestational age.CONCLUSIONS—The upper limit of normal for neonatal CRT was 3 seconds. Nursery containers, phototherapy, and observers produced significantly different results, but the differences were not clinically important. CRT values of the midpoints of the sternum and the forehead are the most consistent.     

Effects of cisapride on ventricular depolarization-repolarization and arrhythmia markers in infants

To study prospectively the effects of cisapride on ventricular repolarization, depolarization, and arrhythmia markers in neonates, we determined before and three days after starting cisapride (1 mg/kg/day): corrected QT interval (QTc) and QT dispersion (QTd) on standard ECGs, and duration of filtered QRS (fQRS) and of low amplitude (<40 microV) terminal signals (LAS40, ms) and root mean square of the last 40 ms (RMS40, microV) using high-gain signal-averaged ECG (SAECG). Twenty-four term and 11 preterm infants (gestational age 23-35 weeks) were studied at a median chronological age of 32 days. QTc and QTd were not different between term and preterm infants. Cisapride lengthened QTc (mean +/- SD; ms: 396.6 +/- 24.8 before vs. 417.0 +/- 35.2 after, p < 0.001). Three term and two preterm infants (5/35 = 14%; 95% CI: 5-30%) had a QTc >450 ms after cisapride. QTd after cisapride increased significantly in all infants with prolonged QTc. Filtered QRS, LAS40, and RMS40 before and after cisapride were within our normal values. We conclude that cisapride prolongs ventricular repolarization in neonates and infants without altering depolarization. Although no clinical arrhythmias were observed the dose of 0.8 mg/kg/day should not be exceeded.     

Randomised controlled trial of the effect of cisapride on the pyloric muscle in preterm infants

In this study we determined the effects of cisapride on the pyloric muscle in preterm infants. To perform a randomised, double blind, placebo controlled study, two groups each of 16 preterm newborns were given either cisapride (0.2 mg/kg every 8 h) or a placebo for at least 7 days. Infants were studied first on the day when treatment with cisapride or placebo was to be initiated (time 0), and then after 3 (time 1) and 7 days (time 2). In each group, the following parameters were studied by ultrasonography: cross-sectional diameter of the entire pylorus, muscle thickness, and length of the pyloric canal. Also, the mean daily total gastric aspirate volume was studied for the entire week of the study. At time 0, we observed no significant differences between the two groups with respect to diameter, muscle thickness and length of the pyloric muscle. At time 1 and time 2, both diameter and muscle thickness were significantly greater in the cisapride group than in the placebo group. Furthermore, the length of the pyloric canal was significantly greater in the cisapride group than in placebo group at time 2, though not so at time 1. For the entire week of the study, we found a significantly larger mean daily total gastric aspirate volume in the group of infants treated with cisapride compared to the placebo treated group. CONCLUSION: Cisapride significantly affects all of the main measurements of the pyloric muscle and causes a significantly larger amount of daily total gastric aspirate volume. Its use to promote feeding intolerance in preterm newborns cannot be recommended.     

Neonatal seizures associated with cerebral lesions shown by magnetic resonance imaging

AIM—To determine the diagnostic potential of magnetic resonance imaging (MRI) in neonatal seizures; to elucidate the aetiology, timing, and prognosis of the cerebral lesions detected.METHODS—Thirty one term neonates with clinical seizures underwent ultrasonography between days 1-7 (mean 2.5 days) and a high field spin-echo MRI scan on days 1-30 (mean 8.1 days), both of which were repeated at 3 months of age. Routine investigation excluded, as far as possible, infection, haematological, and metabolic-toxic causes as causes of the neonatal seizures.RESULTS—Brain abnormality was demonstrated by MRI in 68% of infants and ultrasonographically in 10%. Diffuse brain lesions (present in 29%) were associated with high mortality (58%) and morbidity (42%), whatever the aetiology. In contrast to a better short term prognosis for neonates with focal lesions where no infants died, 33 % had a handicap, and the rest were normal at a mean follow up age of 21/2 years. Cerebral lesions were presumed to have antepartum origin in 43% of cases. Seizure aetiology was considered to be hypoxic-ischaemic in 35%, haemorrhagic in 26%, metabolic disturbances and cerebral dysgenesis in 16% and unknown in 23%.CONCLUSIONS—MRI detected a remarkably high incidence of brain lesions in neonatal seizures. Almost half of these were of prenatal origin and pathogenesis may essentially be attributed to hypoxic and/or haemodynamic causes.     

The probiotic <Emphasis Type="Italic">Escherichia coli</Emphasis> strain Nissle 1917 (EcN) stops acute diarrhoea in infants and toddlers

In most cases, acute diarrhoea will become self-limiting during the first few days after onset. For young children, however, health risks may develop when the disease lasts longer than 3 days. The purpose of the present trial was to determine whether the stool frequency of infants and toddlers suffering from acute diarrhoea could be normalised more quickly by administering the probiotic Escherichia coli Nissle 1917 (EcN) solution than by administering a placebo. The safety of EcN were also assessed. A total of 113 children (aged 2–47 months) with acute diarrhoea (> three watery or loose stools in 24 h) were randomised to either a group receiving the probiotic EcN suspension (n = 55) or a group receiving the placebo suspension (n = 58) in a confirmative, double-blind clinical trial. Depending on the age of patients, 1–3 ml per day of verum suspension (10⁸ viable EcN cells per millilitre) or placebo were administered orally. The causes of the diarrhoea were viral rather than bacterial, but they were mainly unspecific infections. The median onset of treatment response (reduction of daily stool frequency to ≤ three watery or loose stools over at least 2 consecutive days) occurred more rapidly in the children receiving the EcN solution (2.5 days) than in those receiving the placebo (4.8 days), a significant difference (2.3 days; p = 0.0007). The number of patients showing a response was clearly higher (p < 0.0001) in the EcN group (52/55; 94.5%) than in the placebo group (39/58; 67.2%). EcN was found to be safe and well-tolerated, and it showed a significant superiority compared to the placebo in the treatment of acute diarrhoea in infants and toddlers. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Supported by ARDEYPHARM through the provision of verum and placebo medication and reimbursement of study-related expenditure. The authors would like to thank all hospital staff members, clinical monitors and parents for contributing to the work achieved.     

Changes in oxygenation and pulmonary haemodynamics in preterm infants treated with inhaled nitric oxide

AIM—To investigate changes in various cardiorespiratory variables with inhaled nitric oxide (NO), as part of a randomised controlled trial.METHODS—Infants were treated with inhaled NO for 72 hours. Changes in oxygenation were assessed using the oxygenation index (OI). Serial changes in pulmonary artery pressure (PAP) were assessed using the Doppler derived acceleration time to right ventricular ejection time ratio (AT:RVET). Doppler measurements of right ventricular output, pulmonary blood flow, and systolic PAP was performed in a subset of infants.RESULTS—Twenty infants received inhaled NO and 22 acted as controls. Infants were treated at a median dose of 5 (range 5 to 20) ppm. There was a fall in median OI by 17% in treated infants within 30 minutes of treatment. The fall in OI in treated infants was significantly different from the response in controls until 96 hours. Infants treated with inhaled NO showed a rapid response with a median rise in AT:RVET of 0.04 (range ?0.06 to 0.12) within 30 minutes. The change in AT:RVET was significantly different from controls until 4 hours. Median systolic PAP also fell in treated infants by 6.1 (range ?14.4 to ?4.4) mm Hg within 1 hour. Changes in OI were significantly associated with changes in PBF (r = 0.44), but not with changes in AT:RVET.CONCLUSION—Treatment with inhaled NO rapidly improves oxygenation and lowers PAP in preterm infants. However, these effects are transient and treatment does not influence long term outcome.     

Randomised controlled trial of acetate in preterm neonates receiving parenteral nutrition

AIMS—To determine whether by partly replacing chloride with acetate in parenteral nutrition, hyperchloraemia, metabolic acidosis, and the subsequent use of interventions such as colloid infusion, alkali treatment, increased assisted ventilation, would be reduced.
METHODS—Fifty eight neonates of less than 32 weeks gestation, receiving parenteral nutrition from days 3 to 10, were given either standard parenteral nutrition or a novel formulation with replacement of any chloride dose > 3 mmol/kg/day as acetate.
RESULTS—Acetate (0 to 14.2 mmol/kg/day) reduced the incidence of hyperchloraemia from 77% to 25%, and caused an increase in base excess from day 5 onwards (mean intergroup difference 3.6 to 9.9 mmol/l), an increased pH (day 8, 7.34 vs 7.26), with an increased pCO₂ (1 kPa). The acetate group received less bicarbonate (median 0 mmol vs 4.8 mmol) and less colloid (41 ml/kg vs 204 ml/kg). There was no difference in any parameter of assisted ventilation.
CONCLUSION—Acetate in neonatal parenteral nutrition reduces metabolic acidosis and hyperchloraemia.