Deadspace estimation from CO2 versus molar mass measurements in infants

BACKGROUND: Estimation of respiratory deadspace is often based on the CO2 expirogram, however presence of the CO2 sensor increases equipment deadspace, which in turn influences breathing pattern and calculation of lung volume. In addition, it is necessary to correct for the delay between the sensor and flow signals. We propose a new method for estimation of effective deadspace using the molar mass (MM) signal from an ultrasonic flowmeter device, which does not require delay correction. We hypothesize that this estimation is correlated with that calculated from the CO2 signal using the Fowler method. METHODS: Breath-by-breath CO2, MM and flow measurements were made in a group of 77 term-born healthy infants. Fowler deadspace (Vd,Fowler) was calculated after correcting for the flow-dependent delay in the CO2 signal. Deadspace estimated from the MM signal (Vd,MM) was defined as the volume passing through the flowhead between start of expiration and the 10% rise point in MM. RESULTS: Correlation (r = 0.456, P < 0.0001) was found between Vd,MM and Vd,Fowler averaged over all measurements, with a mean difference of -1.4% (95% CI -4.1 to 1.3%). Vd,MM ranged from 6.6 to 11.4 ml between subjects, while Vd,Fowler ranged from 5.9 to 12.0 ml. Mean intra-measurement CV over 5-10 breaths was 7.8 +/- 5.6% for Vd,MM and 7.8 +/- 3.7% for Vd,Fowler. Mean intra-subject CV was 6.0 +/- 4.5% for Vd,MM and 8.3 +/- 5.9% for Vd,Fowler. Correcting for the CO2 signal delay resulted in a 12% difference (P = 0.022) in Vd,Fowler. Vd,MM could be obtained more frequently than Vd,Fowler in infants with CLD, with a high variability. CONCLUSIONS: Use of the MM signal provides a feasible estimate of Fowler deadspace without introducing additional equipment deadspace. The simple calculation without need for delay correction makes individual adjustment for deadspace in FRC measurements possible. This is especially important given the relative large range of deadspace seen in this homogeneous group of infants.

Isolation of human bocavirus from Swiss infants with respiratory infections

Human bocavirus (HBoV) is a novel agent associated with respiratory symptoms in adults and children. We studied prospectively the first acute respiratory infection in a birth cohort of healthy neonates in Switzerland. HBoV was identified in 5 (4.5%) of 112 infants as young as 3 months of age. In 4 of the 5 infants, HBoV was associated with other respiratory viruses. We conclude that HBoV circulates in the community and is acquired early in life.

Frequent atrial premature beats predict paroxysmal atrial fibrillation in stroke patients: an opportunity for a new diagnostic strategy

BACKGROUND AND PURPOSE: For patients having suffered ischemic stroke, the current diagnostic strategies often fail to detect atrial fibrillation as a potential cause of embolic events. The aim of the study was to identify paroxysmal atrial fibrillation in stroke patients. We hypothesized that patients with frequent atrial premature beats (APBs) recorded in 24-hour ECG will show more often atrial fibrillation when followed by repeated long-term ECG recordings than patients without or infrequent APBs. METHODS: 127 patients with acute ischemic stroke and without known AF were enrolled in a prospective study to detect paroxysmal AF. Patients were stratified according to the number of APBs recorded in a 24-hour ECG (> or =70 APBs versus <70 APBs). Subsequently, they all underwent serial 7-day event-recorder monitoring at 0, 3, and 6 months. RESULTS: Serial extended ECG monitoring identified AF in 26% of patients with frequent APBs but only in 6.5% when APBs were infrequent (P=0.0021). A multivariate analysis showed that the presence of frequent APBs in the initial 24-hour ECG was the only independent predictor of paroxysmal AF during follow-up (odds ratio 6.6, 95% confidence intervals 1.6 to 28.2, P=0.01). CONCLUSIONS: In patients with acute ischemic stroke, frequent APBs (> or = 70/24 hours) are a marker for individuals who are at greater risk to develop or have paroxysmal AF. For such patients, we propose a diagnostic workup with repeated prolonged ECG monitoring to diagnose paroxysmal AF.

Nanoduct(R) sweat testing for rapid diagnosis in newborns, infants and children with cystic fibrosis

Determination of chloride concentration in sweat is the current diagnostic gold standard for Cystic Fibrosis (CF). Nanoduct(R) is a new analyzing system measuring conductivity which requires only 3 microliters of sweat and gives results within 30 minutes. The aim of the study was to evaluate the applicability of this system in a clinical setting of three children's hospitals and borderline results were compared with sweat chloride concentration. Over 3 years, 1,041 subjects were tested and in 946 diagnostic results were obtained. In 95 children, Nanoduct(R) failed (9.1% failure rate), mainly due to failures in preterm babies and newborns. Assuming 59 mmol/L as an upper limit of normal conductivity, all our 46 CF patients were correctly diagnosed (sensitivity 100%, 95% CI: 93.1-100; negative predicted value 100% (95% CI: 99.6-100) and only 39 non CF's were false positive (39/900, 4.3%; specificity 95.7%, 95%CI: 94.2-96.9, positive predicted value 54.1% with a 95%CI: 43.4-65.0). Increasing the diagnostic limit to 80 mmol/L, the rate fell to 0.3% (3/900). CF patients had a median conductivity of 115 mmol/L; the non-CF a median of 37 mmol/L. In conclusion, the Nanoduct(R) test is a reliable diagnostic tool for CF diagnosis: It has a failure rate comparable to other sweat tests and can be used as a simple bedside test for fast and reliable exclusion, diagnosis or suspicion of CF. In cases with borderline conductivity (60-80 mmol/L) other additional methods (determination of chloride and genotyping) are indicated.

Expression of Plasmodium falciparum 3D7 STEVOR proteins for evaluation of antibody responses following malaria infections in naïve infants

Clinical immunity to Plasmodium falciparum malaria develops after repeated exposure to the parasite. At least 2 P. falciparum variant antigens encoded by multicopy gene families (var and rif) are targets of this adaptive antibody-mediated immunity. A third multigene family of variant antigens comprises the stevor genes. Here, 4 different stevor sequences were selected for cloning and expression in Escherichia coli and His6-tagged fusion proteins were used for assessing the development of immunity. In a cross-sectional analysis of clinically immune adults living in a malaria endemic area in Ghana, high levels of anti-STEVOR IgG antibody titres were determined in ELISA. A cross-sectional study of 90 nine-month-old Ghanaian infants using 1 recombinant STEVOR showed that the antibody responses correlated positively with the number of parasitaemia episodes. In a longitudinal investigation of 17 immunologically naïve 9-month-old infants, 3 different patterns of anti-STEVOR antibody responses could be distinguished (high, transient and low). Children with high anti-STEVOR-antibody levels exhibited an elevated risk for developing parasitaemia episodes. Overall, a protective effect could not be attributed to antibodies against the STEVOR proteins chosen for the study presented here.

Lung volume, breathing pattern and ventilation inhomogeneity in preterm and term infants

BACKGROUND: Morphological changes in preterm infants with bronchopulmonary dysplasia (BPD) have functional consequences on lung volume, ventilation inhomogeneity and respiratory mechanics. Although some studies have shown lower lung volumes and increased ventilation inhomogeneity in BPD infants, conflicting results exist possibly due to differences in sedation and measurement techniques. METHODOLOGY/PRINCIPAL FINDINGS: We studied 127 infants with BPD, 58 preterm infants without BPD and 239 healthy term-born infants, at a matched post-conceptional age of 44 weeks during quiet natural sleep according to ATS/ERS standards. Lung function parameters measured were functional residual capacity (FRC) and ventilation inhomogeneity by multiple breath washout as well as tidal breathing parameters. Preterm infants with BPD had only marginally lower FRC (21.4 mL/kg) than preterm infants without BPD (23.4 mL/kg) and term-born infants (22.6 mL/kg), though there was no trend with disease severity. They also showed higher respiratory rates and lower ratios of time to peak expiratory flow and expiratory time (t(PTEF)/t(E)) than healthy preterm and term controls. These changes were related to disease severity. No differences were found for ventilation inhomogeneity. CONCLUSIONS: Our results suggest that preterm infants with BPD have a high capacity to maintain functional lung volume during natural sleep. The alterations in breathing pattern with disease severity may reflect presence of adaptive mechanisms to cope with the disease process.

Development of the premature infant nose throat-model (PrINT-Model): an upper airway replica of a premature neonate for the study of aerosol delivery

Clinical efficacy of aerosol therapy in premature newborns depends on the efficiency of delivery of aerosolized drug to the bronchial tree. To study the influence of various anatomical, physical, and physiological factors on aerosol delivery in preterm newborns, it is crucial to have appropriate in vitro models, which are currently not available. We therefore constructed the premature infant nose throat-model (PrINT-Model), an upper airway model corresponding to a premature infant of 32-wk gestational age by three-dimensional (3D) reconstruction of a three-planar magnetic resonance imaging scan and subsequent 3D-printing. Validation was realized by visual comparison and comparison of total airway volume. To study the feasibility of measuring aerosol deposition, budesonide was aerosolized through the cast and lung dose was expressed as percentage of nominal dose. The airway volumes of the initial magnetic resonance imaging and validation computed tomography scan showed a relative deviation of 0.94%. Lung dose at low flow (1 L/min) was 61.84% and 9.00% at high flow (10 L/min), p < 0.0001. 3D-reconstruction provided an anatomically accurate surrogate of the upper airways of a 32-wk-old premature infant, making the model suitable for future in vitro testing.

Regional and overall ventilation inhomogeneities in preterm and term-born infants

OBJECTIVES: We compared ventilation inhomogeneity assessed by electrical impedance tomography (EIT) and multiple breath washout (MBW) in preterm and term-born infants. We hypothesised that EIT measurements in spontaneously breathing infants are repeatable and that differences in regional ventilation distribution measured by EIT can distinguish between preterm and term-born infants. DESIGN: Cross-sectional group comparison study. SETTING: Lung function laboratory at a University Children's Hospital. PARTICIPANTS: Seventeen healthy term-born and 15 preterm infants at a matched postmenstrual age of 44 weeks. MEASUREMENTS AND RESULTS: We concurrently measured ventilation inhomogeneity by EIT, ventilation inhomogeneity (LCI) and functional residual capacity (FRC) by MBW and tidal breathing variables during unsedated quiet sleep. EIT measurements were highly repeatable (coefficient of variation 3.6%). Preterm infants showed significantly more ventilation of the independent parts of the lungs compared to healthy term-born infants assessed by EIT (mean difference 5.0, 95 CI 1.3-8%). Whereas the two groups showed no differences in lung volumes or ventilation inhomogeneities assessed by MBW, EIT discriminated better between term and preterm infants. (FRC/kg: mean difference 1.1 mL, 95% CI -1.4-3.8 mL; LCI: mean difference 0.03, 95% CI -0.32-0.25). CONCLUSIONS: EIT shows distinct differences in ventilation distribution between preterm and term-born infants, which cannot be detected by MBW. Although preterm infants are capable of dynamically maintaining overall functional residual volume and ventilation distribution, they show some spatial differences from fullterm infants.

Pain relief in ventilated preterms during endotracheal suctioning: a randomized controlled trial

BACKGROUND: In Switzerland approximately 8% of infants are born prematurely. Some of them undergo mechanical ventilation including endotracheal suctioning (ETS). ETS is one of the most frequently performed interventions and is linked to stress and pain, but its treatment is controversial. In Switzerland there is a lack of standardisation in pain relief for ETS. AIMS: To test the hypothesis that an intermittent dose of morphine reduces pain during ETS and that subsequent multisensorial stimulation (MSS), as a non pharmacological comforting intervention, helps infants to recover from experienced pain. METHOD: A randomized placebo controlled trial in two tertiary neonatal intensive care units (NICU) with a sample of 30 mechanically ventilated preterm infants was conducted. Pain was measured by three pain assessment tools (Bernese Pain Scale for Neonates, Premature Infant Pain Profile and Visual Analogue Scale) RESULTS: Morphine did not lead to any pain relief from ETS as measured by three pain scales. Nor did the comforting intervention of MSS show any effect. Repeated-measure analysis of variance for the within and between groups comparison showed no statistical significance. CONCLUSIONS: The administration of morphine for pain relief in ventilated preterm neonates during ETS remains questionable and the use of MSS as a comforting intervention after painful stimulus cannot be recommended. The validity testing of the instruments for this patient population should undergo a systematic validation trajectory. Future research should focus on options among non pharmacological interventions for relieving pain during ETS.

The Ross procedure in infants and young children

BACKGROUND: This study reviews our experience with the Ross procedure in infants and young children. METHODS: From September 1993 to September 2004, 52 children less than 15 years of age underwent a Ross procedure. The patients ranged in age from 4 days to 15 years old (median, 5 years). Fifteen patients (29%) were less than 2 years of age. The predominant indication for the Ross procedure was aortic stenosis. Sixteen patients underwent a Ross-Konno procedure for severe left ventricular outflow tract obstruction. Thirty-four patients had 48 previous interventions. Preoperatively, 6 patients showed severe left ventricular dysfunction, and 2 of the patients required ventilation and inotropic support. Concomitant procedures were performed in 8 patients. Three patients had a mitral valve replacement, 2 patients had a ventricular septal defect closure and an aortic arch reconstruction, 2 patients had aortic arch reconstructions, and 1 patient had resection of a coarctation and a ventricular septal defect closure. RESULTS: Patients were followed up for a median of 43 months (range, 1 to 130). Overall survival was 85% +/- 5% at 1 and 82% +/- 5% at 2, 5, and 10 years. Hospital mortality was 5 of 52 patients (9.6%). All deaths occurred in neonates or infants less than 2 months of age, who needed urgent surgery. Three patients died late of noncardiac causes. At last follow-up, all patients were classified in New York Heart Association functional class I or II. No patient had endocarditis of the autograft or the right ventricular outflow tract replacement. During the follow-up, no event of thrombembolism was observed. No patient required the insertion of a permanent pacemaker. Overall freedom from reoperation is 57% +/- 15% at 10 years. One patient required the replacement of the autograft at 6 months postoperatively. The development of mild aortic insufficiency was observed in 24 patients, and moderate aortic insufficiency in 1 patient during follow-up. Freedom from reoperation for the right ventricular outflow tract replacement is 60% +/- 15% at 10 years. CONCLUSIONS: The Ross procedure represents an attractive approach to aortic valve disease in young children. However, a high early mortality rate has to be considered when performing this procedure in neonates or infants who present in critical preoperative condition.

Postoperative sepsis in infants below 6 months of age

BACKGROUND: Sepsis is a threatening postoperative complication especially in small infants. Regarding the advances in perinatal medicine, its incidence is unknown to date. We aimed to investigate the incidence, risk factors, laboratory findings and outcome of postoperative sepsis in infants younger than 6 months old. METHODS: We examined postoperative sepsis in babies below 6 months of age during a 4-year period at a tertiary pediatric institution. RESULTS: The rate of postoperative sepsis was 6.9%. Laparotomy with enterotomy, thoracotomy and diaphragmatic hernia repair (P<0.05, respectively) as well as low postnatal age and long operation time (P<0.001, respectively) were correlated with the incidence of sepsis. Significant independent predictors for the development of sepsis were the presence of a central venous catheter and perioperative antibiotic treatment (P<0.001, respectively). Coagulase negative Staphylococci were the major infecting organism associated with postoperative sepsis, accounting for 53% of monomicrobial infections. Complete blood counts with differential were not different between infants with sepsis and controls, who had undergone the same surgical procedures. Outcome was favorable in all cases; however, the length of hospital stay was significantly longer in sepsis patients (P<0.05). CONCLUSIONS: Postoperative sepsis syndrome is a frequent complication in infants below 6 months of age and causes significant prolongation of hospital stay. Adequate prevention and therapeutic strategies warrant further prospective investigations.