Mechanical Ventilation in Pediatric and Neonatal Patients.

Pediatric acute respiratory distress syndrome (PARDS) remains a significant cause of morbidity and mortality, with mortality rates as high as 50% in children with severe PARDS. Despite this, pediatric lung injury and mechanical ventilation has been poorly studied, with the majority of investigations being observational or retrospective and with only a few randomized controlled trials to guide intensivists. The most recent and universally accepted guidelines for pediatric lung injury are based on consensus opinion rather than objective data. Therefore, most neonatal and pediatric mechanical ventilation practices have been arbitrarily adapted from adult protocols, neglecting the differences in lung pathophysiology, response to injury, and co-morbidities among the three groups. Low tidal volume ventilation has been generally accepted for pediatric patients, even in the absence of supporting evidence. No target tidal volume range has consistently been associated with outcomes, and compliance with delivering specific tidal volume ranges has been poor. Similarly, optimal PEEP has not been well-studied, with a general acceptance of higher levels of F i O2 and less aggressive PEEP titration as compared with adults. Other modes of ventilation including airway pressure release ventilation and high frequency ventilation have not been studied in a systematic fashion and there is too little evidence to recommend supporting or refraining from their use. There have been no consistent outcomes among studies in determining optimal modes or methods of setting them. In this review, the studies performed to date on mechanical ventilation strategies in neonatal and pediatric populations will be analyzed. There may not be a single optimal mechanical ventilation approach, where the best method may simply be one that allows for a personalized approach with settings adapted to the individual patient and disease pathophysiology. The challenges and barriers to conducting well-powered and robust multi-institutional studies will also be addressed, as well as reconsidering outcome measures and study design.

A comparison of the pharmacokinetics of two dosing regimens of cisapride and their effects on corrected QT interval in premature infants.

OBJECTIVE: To compare the pharmacokinetics of two dosing regimens of cisapride and their effects on QT(c) interval. DESIGN: Thirty-one pre-term infants were enrolled in two neonatal intensive care units. In 16 infants, cisapride was started at 0.2 mg/kg orally every 6 h (group A) and in 15 infants at 0.1 mg/kg orally every 3 h (group B). Electrocardiograms were performed before and after 72 h of treatment to calculate the QT(c) interval according to the Bazett formula. After 72 h of treatment, cisapride and norcisapride trough concentrations, and concentrations 1 h after the next cisapride administration were quantified in serum. A linear regression analysis was performed to analyse the effect of postnatal and postconception age. RESULTS: At the start of cisapride treatment, mean postnatal age was 22.9+/-13.9 days (mean+/-SD) for group A and 23.3+/-15.0 days for group B, and mean postconception age was 34.0+/-1.8 weeks for group A and 33.3+/-0.8 weeks for group B. The QT(c) interval increased equally in both groups (group A: +37+/-20 ms, and group B: + 38+/-25 ms; P=0.9). Mean concentration of cisapride 1 h after administration was, as expected from the dosing regimen, significantly higher in group A than in group B (123.7+/-43.2 ng/ml versus 86.7+/-27.8 ng/ml; P=0.03).The difference in trough concentration was not significant (107.4+/-44.3 ng/ml versus 78.2+/-35.4 ng/ml; P=0.09). There was a positive correlation between QT(c) prolongation and cisapride serum concentration (peak: R(2)=0.20, P=0.015; trough: R(2)=0.24, P=0.008) and an inverse correlation between postnatal age and concentration 1 h after administration concentration of cisapride (R(2)=0.19, P=0.02). No correlation was found for postconception age. CONCLUSION: Postnatal age has an inverse relationship with cisapride serum concentration in premature infants, whereas postconception age is not correlated. The maturation process of the biotransformation system of cisapride during the first weeks of life, triggered by birth, but independent of gestational age at birth can explain this observation. The effect of cisapride on cardiac repolarisation is positively related with the cisapride serum concentration. Administering cisapride every 3 h instead of every 6 h could be advantageous, as it is associated with lower peak cisapride serum concentrations. Further investigations are required to confirm this and its potential clinical benefit on QT(c )and arrhythmia risk.

The T wave as a marker of dispersion of ventricular repolarization in premature infants before and while on treatment with the I(Kr) channel blocker cisapride.

AIMS: Measurement of electrocardiographic intervals to assess dispersion in ventricular repolarization may be helpful in the assessment of the risk of ventricular arrhythmia. We measured QTc, QT dispersion, and T wave intervals in premature infants before and while on treatment with the I(Kr) blocker cisapride as markers for dispersion in ventricular repolarization. METHODS AND RESULTS: We enrolled 15 non-ventilated premature infants with a mean gestational age of 30.5 weeks, ranging from 26.5 to 33.5 weeks, and mean postnatal age of 24 days, with a range from 5 to 51 days. A digital 12 lead electrocardiogram was recorded prior to and 3 days after administering cisapride at a dose of 0.8 mg/kg/day. Serum electrolytes were simultaneously measured. Electrocardiographic measurements before and after included: QT, QTc Bazett, QT dispersion, R-R, T wave interval peak to end, T wave interval peak to end/onset Q to T wave peak, T wave axis, T wave maximum voltage and QRS-T angle. A paired t test and analysis of variance was used to compare the variables before and during treatment. The QTc, T wave interval peak to end and the ratio T wave interval peak to end/onset Q to T peak increased significantly following treatment with cisapride. Results expressed as before and during treatment were for QTc: 429 (65) ms versus 454 (29) ms p < 0.02; for T wave interval peak to end: 65 (11) ms versus 103 (24) p <0.01, for the ratio T wave interval peak to end/onset Q to T peak: 0.32 (0.06) versus 0.55 (0.16) p < 0.001. Treatment with the I(Kr) blocker did not significantly alter the QT dispersion, T wave voltage, angle or QRS-T angle. CONCLUSION: The interval from the peak to the end of the T wave and the ratio of this value to the onset Q to T peak interval, represents regional dispersion of repolarization across the ventricular wall. This is a potentially useful clinical index in the assessment of arrhythmic risk in premature infants being treated by blockade of the I(Kr) channels.

Measurement of interleukin 8 in combination with C-reactive protein reduced unnecessary antibiotic therapy in newborn infants: a multicenter, randomized, controlled trial.

OBJECTIVE: Neonatal bacterial infections carry a high mortality when diagnosed late. Early diagnosis is difficult because initial clinical signs are nonspecific. Consequently, physicians frequently prescribe antibiotic treatment to newborn infants for fear of missing a life-threatening infection. This study was designed to test the hypotheses that a diagnostic algorithm that includes measurements of interleukin 8 (IL-8) and C-reactive protein (CRP) 1) reduces antibiotic therapy and 2) does not result in more initially missed infections compared with standard management that does not include an IL-8 measurement. METHODS: Term and preterm infants who were <72 hours of age and had clinical signs or obstetric risk factors suggesting neonatal bacterial infection but stable enough to wait for results of diagnostic tests were enrolled into the study. A total of 1291 infants were randomly assigned to receive antibiotic therapy according to the guidelines of each center (standard group) or to receive antibiotic therapy when IL-8 was >70 pg/mL and/or CRP was >10 mg/L (IL-8 group). The primary outcome variables were 1) the number of infants treated with antibiotics and 2) the number of infants with infections missed at the initial evaluation. RESULTS: In the IL-8 group, fewer infants received antibiotic therapy than in the standard group (36.1% [237 of 656] vs 49.6% [315 of 635]). In the IL-8 group, 24 (14.5%) of 165 infants with infection were not detected at the initial evaluation, compared with 28 (17.3%) of 162 in the standard group. CONCLUSIONS: The number of newborn infants who received postnatal antibiotic therapy can be reduced with a diagnostic algorithm that includes measurements of IL-8 and CRP. This diagnostic strategy seemed to be safe.