The utility of point-of-care ultrasound protocol to confirm central venous catheter placement in the preterm infant.

Central vascular access is frequently required for preterm infants. Confirmation of positioning of central line is typically on chest and abdominal radiographs; POCUS is a relatively novel diagnostic method. Misdiagnosis is the main concern limiting use of this modality. The aim of this study is to validate our standard protocol accuracy in locating the central catheter position by correlating catheter position as determined by POCUS with radiographs. Premature babies < or equal to 30 weeks gestation who had peripheral central lines or surgical lines were enrolled. Confirmation of line position by radiographs was compared to images obtained through a specific US protocol technique. The operator of US exam was blinded to the radiograph findings. All images were reviewed by two radiologists who were blinded to the radiograph findings. 35 central line placements were assessed. 22 lines were inserted in the UL, and 13 were inserted in the LL with a total of 91 ultrasound scans and radiographs. The position of the line was interpreted as normal in 79/91 scans with interpreter reliability of [Formula: see text]=0.778 (p < 0.001), sensitivity of 0.83 and specificity of 0.96, and positive predictive value of 0.77 and negative predictive value of 0.97. There was no significant difference between the ultrasound interpretation and the radiograph interpretation of UL and LL.  Conclusion: The protocol of POCUS that we propose is a reliable tool for assessing the central line positions in preterm infants. What is Known: • POCUS is a reliable tool assessing the central line positions in preterm infants. What is New: • The protocol of POCUS that we propose is a reliable tool for assessing the central line positions in preterm infants.

Variation in Positive End-Expiratory Pressure Levels for Mechanically Ventilated Extremely Low Birth Weight Infants.

OBJECTIVE: To test the hypothesis that significant positive end-expiratory pressure (PEEP) level variation exists between neonatal centers. STUDY DESIGN: We performed a secondary analysis cohort study of the Nasal Intermittent Positive-Pressure Ventilation trial. Our study population was extremely low birth weight infants requiring mechanical ventilation within 28 days of life. The exposure was neonatal center; 34 international centers participated in the trial. Subjects from centers with fewer than 5 eligible cases were excluded. The main outcome was the maximal PEEP level used during the first course of mechanical ventilation. Infant characteristics judged a priori to directly influence clinical PEEP level selection and all characteristics associated with PEEP at P <.05 in bivariable analyses were included with and without center in multivariable linear regression models. Variation in PEEP level use between centers following adjustment for infant characteristics was assessed. RESULTS: A total of 278 extremely low birth weight infants from 17 centers were included. Maximal PEEP ranged from 3 to 9 cm H2O, mean = 5.7 (SD = 0.9). Significant variation between centers remained despite adjustment for infant characteristics (P < .0001). Further, center alone explained a greater proportion of the PEEP level variation than all infant characteristics combined. CONCLUSIONS: Marked variation in PEEP levels for extremely low birth weight infants exists between neonatal centers. Research providing evidence-based guidance for this important aspect of respiratory care in preterm infants at high risk of lung injury is needed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00433212.

A comparison of bilevel and ventilator-delivered non-invasive respiratory support.

OBJECTIVE: To compare the rates of death or bronchopulmonary dysplasia (BPD) in infants who received nasal intermittent positive pressure ventilation (NIPPV) delivered by a conventional mechanical ventilator (CMV) or a bilevel device. DESIGN: A preplanned non-randomised comparison of infants randomised to the NIPPV arm of the NIPPV trial. SETTING: Thirty-six tertiary neonatal units in three continents. PATIENTS: Infants <1000 g and <30 weeks gestational age at birth. INTERVENTIONS: Infants received treatment with CMV NIPPV or bilevel NIPPV, as a primary mode of respiratory support or following first extubation. RESULTS: 241 received mainly bilevel NIPPV and 215 mainly CMV NIPPV. No difference was found in death or BPD at 36 weeks corrected age (adjusted OR 0.88 (95% CI 0.57 to 1.35)). More deaths occurred in infants receiving bilevel NIPPV (9.4%) than in CMV NIPPV (2.3%) (adjusted OR 5.01: 95% CI 1.74 to 14.4). There was a corresponding but not statistically significant decrease in BPD in the bilevel NIPPV group (30% vs 37%) (adjusted OR 0.64 (95% CI 0.41 to 1.02)). No difference was observed in extubation failure or age at last extubation. A post hoc test of interaction between device type and synchronisation was not statistically significant. CONCLUSIONS: We did not observe a statistically significant difference in the composite outcome of death or BPD between infants who received mostly bilevel NIPPV compared with mostly CMV NIPPV. Differences in component outcomes of morbidity and BPD may be due to the competing nature of these outcomes or differences in baseline characteristics of infants. TRIAL REGISTRATION NUMBER: NCT00433212.

A trial comparing noninvasive ventilation strategies in preterm infants.

BACKGROUND: To reduce the risk of bronchopulmonary dysplasia in extremely-low-birth-weight infants, clinicians attempt to minimize the use of endotracheal intubation by the early introduction of less invasive forms of positive airway pressure. METHODS: We randomly assigned 1009 infants with a birth weight of less than 1000 g and a gestational age of less than 30 weeks to one of two forms of noninvasive respiratory support--nasal intermittent positive-pressure ventilation (IPPV) or nasal continuous positive airway pressure (CPAP)--at the time of the first use of noninvasive respiratory support during the first 28 days of life. The primary outcome was death before 36 weeks of postmenstrual age or survival with bronchopulmonary dysplasia. RESULTS: Of the 497 infants assigned to nasal IPPV for whom adequate data were available, 191 died or survived with bronchopulmonary dysplasia (38.4%), as compared with 180 of 490 infants assigned to nasal CPAP (36.7%) (adjusted odds ratio, 1.09; 95% confidence interval, 0.83 to 1.43; P=0.56). The frequencies of air leaks and necrotizing enterocolitis, the duration of respiratory support, and the time to full feedings did not differ significantly between treatment groups. CONCLUSIONS: Among extremely-low-birth-weight infants, the rate of survival to 36 weeks of postmenstrual age without bronchopulmonary dysplasia did not differ significantly after noninvasive respiratory support with nasal IPPV as compared with nasal CPAP. (Funded by the Canadian Institutes of Health Research; NIPPV ClinicalTrials.gov number, NCT00433212; Controlled-Trials.com number, ISRCTN15233270.).

CO(2) inhalation as a treatment for apnea of prematurity: a randomized double-blind controlled trial.

OBJECTIVE: To compare the effect of prolonged inhalation of a low concentration of CO(2) with theophylline for the treatment of apnea of prematurity. STUDY DESIGN: Prospective, randomized, double-blind controlled trial of 87 preterm infants with apnea of prematurity (27-32 weeks' gestational age) assigned to either theophylline plus 0.5 L/min of room air via nasal prongs or placebo plus 0.5 L/min with CO(2) (about 1% inhaled) by nasal prongs for 3 days. RESULTS: Apnea time significantly decreased in the theophylline group from 189±33 s/h (control) to 57±11, 50±9, and 61±13 (days 1-3) (P=.0001) and in the CO(2) group from 183±44 (control) to 101±26, 105±29, and 94±26 s/h (days 1-3) (P=.03). Seven infants in the CO(2) group but none in the theophylline group failed to complete the study due to severe apneas (P=.003). CONCLUSIONS: Because theophylline was more effective in reducing the number and severity of apneas, inhalation of low concentration of CO(2), as used in the present study, cannot be considered as an alternative to theophylline in the treatment of apnea of prematurity. The less effectiveness of CO(2) treatment may have been related to the variability of the delivery of CO(2).

Evidence of oxidative stress in relation to feeding type during early life in premature infants.

Morbidity in the premature (PT) infant may reflect difficult adaptation to oxygen. We hypothesized that feeding including formula feeding (F) and feeding mother's milk (HM) with added fortifier would affect redox status. Therefore, 65 PT infants (birth weight: 1146 ± 261 g; GA: 29 ± 2.5 wk; mean ± SD) were followed biweekly, once oral feeds were introduced. Feeding groups: F (>75% total feeds) and HM (>75% total feeds) were further subdivided according to human milk fortifier (HMF) content of 0-19, 20-49, and ≥ 50%. Oxidative stress was quantified by F2-isoprostanes (F2-IsoPs) in urine, protein carbonyls, and oxygen radical absorbance capacity (ORAC) in plasma. F2-IsoPs (ng/mg creatinine): 0-2 wk, 125 ± 63; 3-4 wk, 191 ± 171; 5-6 wk, 172 ± 83; 7-8 wk, 211 ± 149; 9-10 wk, 222 ± 121; and >10 wk, 183 ± 67. Protein carbonyls from highest [2.41 ± 0.75 (n = 9)] and lowest [2.25 ± 0.89 (n = 12) pmol/µg protein] isoprostane groups did not differ. ORAC: baseline, 6778 ± 1093; discharge, 6639 ± 735 [full term 4 and 12 M, 9010 ± 600 mg (n = 12) TE]. Highest isoprostane values occurred in infants with >50% of their mother's milk fortified. Further research on HMF is warranted.

The cost-effectiveness of palivizumab for respiratory syncytial virus prophylaxis in premature infants with a gestational age of 32-35 weeks: a Canadian-based analysis .

BACKGROUND: Prophylactic therapy with palivizumab, a humanized monoclonal antibody, has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations in preterm infants, including those in the 32-35 weeks' gestational age (GA) subgroup. The cost-effectiveness of this therapy in Canada is unknown. OBJECTIVES: To evaluate the cost-effectiveness of palivizumab as respiratory syncytial virus prophylaxis in premature infants born at 32-35 weeks' GA. DESIGN: A decision analytic model was designed to compare both direct and indirect medical costs and benefits of prophylaxis in this subgroup of premature infants. Sensitivity analyses were performed to ascertain the robustness of the model for five point estimates: mortality rate, discounting rates, health-utility values, degree of vial-sharing and administration costs. A probabilistic sensitivity analysis (PSA) was also conducted. SETTING: Canadian publicly funded health-care system (Ministry of Health payer perspective) for base-case analysis. Societal perspective, accounting for future lost productivity, was adopted for a secondary analysis. PARTICIPANTS: Canadian infants born at 32-35 weeks' GA without chronic lung disease. INTERVENTIONS: Palivizumab prophylaxis versus no prophylaxis. MAIN OUTCOME MEASURES: Expected costs and incremental cost-effectiveness ratio expressed as cost per life-year gained (LYG) and quality-adjusted life-year (QALY) using 2007 Canadian dollars. RESULTS: The expected costs were higher for palivizumab prophylaxis as compared with no prophylaxis. The incremental cost-effectiveness ratio (ICER) for the base-case scenario was $20 924 per QALY after discounting, which is considered cost-effective in Canada. When the uncertainty of the input parameter assumptions was tested through sensitivity analyses assessing several data sources for five key parameters, no substantial differences were found from the base-case results. The PSA indicated a 0.99 probability that the ICER for palivizumab was less than $50 000/QALY. Sub-analyses that varied the number of risk factors found that for infants with two or more risk factors, or at least moderate risk, palivizumab had incremental costs per QALY that indicated moderate-to-strong evidence for adoption (range: $808-81 331, per QALY). CONCLUSIONS: Palivizumab was cost-effective and the authors' model supports prophylaxis for infants born at 32-35 weeks' GA, particularly those with more than two risk factors or at least a moderate level of risk according to a risk scoring tool.