Congenital diaphragmatic hernia: quality improvement using a maximal lung protection strategy and early surgery-improved survival.

To evaluate the effectiveness of a novel protocol, adopted in our institution, as a quality improvement project for congenital diaphragmatic hernia (CDH). A maximal lung protection (MLP) protocol was implemented in 2019. This strategy included immediate use of high-frequency oscillatory ventilation (HFOV) after birth, during the stay at the Neonatal Intensive Care Unit (NICU), and during surgical repair. HFOV strategy included low distending pressures and higher frequencies (15 Hz) with subsequent lower tidal volumes. Surgical repair was performed early, within 24 h of birth, if possible. A retrospective study of all inborn neonates prenatally diagnosed with CDH and without major associated anomalies was performed at the NICU of Schneider Children's Medical Center of Israel between 2009 and 2022. Survival rates and pulmonary outcomes of neonates managed with MLP were compared to the historical standard care cohort. Thirty-three neonates were managed with the MLP protocol vs. 39 neonates that were not. Major adverse outcomes decreased including death rate from 46 to 18% (p = 0.012), extracorporeal membrane oxygenation from 39 to 0% (p < 0.001), and pneumothorax from 18 to 0% (p = 0.013). CONCLUSION:  MLP with early surgery significantly improved survival and additional adverse outcomes of neonates with CDH. Prospective randomized studies are necessary to confirm the findings of the current study. WHAT IS KNOWN: • Ventilator-induced lung injury was reported as the main cause of mortality in neonates with congenital diaphragmatic hernia (CDH). • Conventional ventilation is recommended by the European CDH consortium as the first-line ventilation modality; timing of surgery is controversial. WHAT IS NEW: • A maximal lung protection strategy based on 15-Hz high-frequency oscillatory ventilation with low distending pressures as initial modality and early surgery significantly reduced mortality and other outcomes.

Late-Onset Sepsis in Very Low Birth Weight Infants.

BACKGROUND AND OBJECTIVES: Late-onset sepsis is associated with significant morbidity and mortality among very low birth weight (VLBW) infants. Our objective was to determine risk factors associated with late-onset sepsis and to present temporal trends in overall and pathogen-specific rates. METHODS: Population-based study by the Israel Neonatal Network on VLBW infants (≤1500 g) born between 1995 and 2019. Late-onset sepsis required clinical symptoms and microbiologic confirmation. Bivariate and multivariable analyses were performed to identify risk factors. The study period was divided into 4 epochs. Overall and pathogen-specific late-onset sepsis rates for each epoch were compared. RESULTS: The study population comprised 31 612 VLBW infants, of whom 7423 (23.5%) had late-onset sepsis. An increased adjusted risk of late-onset sepsis was associated with gestational age <27 w (odds ratio [OR] 8.90, 95% confidence interval [CI] 7.85-10.09) and delivery room resuscitation (OR 1.43, 95% CI 1.34-1.52) and a decreased adjusted risk among infants born between 2013 and 2019 (OR 0.32, 95% CI 0.29-0.35). Late-onset sepsis rates declined from 29.5% in 1995 to 2000 to 13.0% in 2013 to 2019. Gram-negative and fungal rates decreased in all epochs, whereas gram-positive rates decreased only in the last epoch. The adjusted hazard ratios (95% CI) decreased in the 2013 to 2019 versus 1995 to 2000 epochs and were: all late-onset sepsis, 0.40 (0.37-0.43); gram-positive, 0.47 (0.37-0.59); gram- negative, 0.54 (0.48-0.61); fungal, 0.17 (0.12-0.22). CONCLUSIONS: The strongest risk factor for late-onset sepsis was gestational age <27 w. Over a 25-year period, the pathogen-specific rates of late-onset sepsis among VLBW infants decreased approximately twofold for gram-positive and gram-negative bacterial infections and sixfold for fungal infections.

Fetal surgery using fetoscopic endoluminal tracheal occlusion for severe congenital diaphragmatic hernia: a single-center experience.

PURPOSE: To provide a comprehensive report of the experience gained in the prenatal treatment of congenital diaphragmatic hernia (CDH) using fetoscopic endoluminal tracheal occlusion (FETO) following its implementation at a newly established specialized fetal medicine center. METHODS: Mothers of fetuses with severe CDH were offered prenatal treatment by FETO. RESULTS: Between 2018 and 2021, 16 cases of severe CDH underwent FETO. The median gestational age (GA) at balloon insertion was 28.4 weeks (IQR 27.8-28.6). The median GA at delivery was 37 weeks (IQR 34.4-37.8). The survival rate was 8/16 cases (50%). None of the survivors required home oxygen therapy at 6 months of age. Comparison between the survivors and deceased showed that survivors had balloon insertion 1 week earlier (27.8 vs. 28.4 weeks, p = 0.007), a higher amniotic fluid level change between pre- to post-FETO (3.4 vs 1.3, p = 0.024), a higher O/E LHR change between pre- to post-FETO (50.8 vs. 37.5, p = 0.047), and a GA at delivery that was 2 weeks later (37.6 vs. 35.4 weeks, p = 0.032). CONCLUSIONS: The survival rate at 6 months of age in cases of severe CDH treated with FETO in our center was 50%. Our new fetal medicine center matches the performance of other leading international centers.

Overestimation of Oxygen Saturation Measured by Pulse Oximetry in Hypoxemia. Part 1: Effect of Optical Pathlengths-Ratio Increase.

On average, arterial oxygen saturation measured by pulse oximetry (SpO2) is higher in hypoxemia than the true oxygen saturation measured invasively (SaO2), thereby increasing the risk of occult hypoxemia. In the current article, measurements of SpO2 on 17 cyanotic newborns were performed by means of a Nellcor pulse oximeter (POx), based on light with two wavelengths in the red and infrared regions (660 and 900 nm), and by means of a novel POx, based on two wavelengths in the infrared region (761 and 820 nm). The SpO2 readings from the two POxs showed higher values than the invasive SaO2 readings, and the disparity increased with decreasing SaO2. SpO2 measured using the two infrared wavelengths showed better correlation with SaO2 than SpO2 measured using the red and infrared wavelengths. After appropriate calibration, the standard deviation of the individual SpO2-SaO2 differences for the two-infrared POx was smaller (3.6%) than that for the red and infrared POx (6.5%, p < 0.05). The overestimation of SpO2 readings in hypoxemia was explained by the increase in hypoxemia of the optical pathlengths-ratio between the two wavelengths. The two-infrared POx can reduce the overestimation of SpO2 measurement in hypoxemia and the consequent risk of occult hypoxemia, owing to its smaller increase in pathlengths-ratio in hypoxemia.

Antibiotic Discontinuation 24 h After Neonatal Late-Onset Sepsis Work-Up-A Validated Decision Tree Model.

Objectives: Neonatal late-onset sepsis work-up is a frequent occurrence in every neonatal department. Blood cultures are the diagnostic gold standard, however, a negative culture prior to 48-72 h is often considered insufficient to exclude sepsis. We aimed to develop a decision tree which would enable exclusion of late-onset sepsis within 24 h using clinical and laboratory variables. Study Design: Infants evaluated for late-onset sepsis during the years 2016-2019, without major malformations, in a tertiary neonatal center were eligible for inclusion. Blood cultures and clinical and laboratory data were extracted at 0 and 24 h after sepsis work-up. Infants with bacteriologically confirmed late-onset sepsis were compared to matched control infants. Univariate logistic regression identified potential risk factors. A decision tree based on Chi-square automatic interaction detection methodology was developed and validated. Results: The study cohort was divided to a development cohort (105 patients) and a validation cohort (60 patients). At 24 h after initial evaluation, the best variables to identify sepsis were C-reactive protein > 0.75 mg/dl, neutrophil-to-lymphocyte ratio > 1.5 and sick-appearance at 24 h. Use of these 3 variables together with blood culture status at 24 h, enabled identification of all infants that eventually developed sepsis through the decision tree model. Our decision tree has an area under the receiver operating characteristic curve of 0.94 (95% CI: 0.90-0.98). Conclusions: In non-sick appearing infants with a negative blood culture at 24 h and normal laboratory values, sepsis is highly unlikely and discontinuing antibiotics after 24 h is a viable option.

Correlates and Trajectories of Preterm Infant Sucking Patterns and Sucking Organization at Term Age.

BACKGROUND: Premature infants may experience increased difficulty with nutrition and growth. Successful oral feeding is an important factor associated with discharge readiness. Despite the importance of feeding as a growth-fostering process, little empiric evidence exists to guide recommendations for early interventions. PURPOSE: Evaluate whether specific elements of sucking, during preterm initiation of oral feeding, predict sucking organization at corrected term age. METHODS: Sucking performance of 88 preterm infants born between 24 and 34 weeks of post-menstrual age was measured at baseline and term (33-35 and 40 ± 1.5 weeks). Participants were divided into 4 groups (quartiles) based on initial measures of performance including number of sucks, number of bursts, sucks per burst, and maximum pressure. Stability in sucking organization was assessed by comparing changes in infant's quartile location from baseline to term. RESULTS: A correlation between quartile location was observed for mean maximum pressure (PMAX): infants with PMAX in the lowest quartile (poorest performance) were significantly more likely to remain in the lowest quartile at term (P < .000); infants in the highest quartile (best performance) at baseline were significantly more likely to be in the highest quartile at term (P < .000). IMPLICATION FOR PRACTICE: Infants with the weakest sucking pressures at 34 weeks of post-menstrual age continue to be at risk for less than optimal feeding skills at 40 weeks of post-menstrual age. Early identification of at-risk infants may allow for effective interventions to potentially decrease long-term feeding problems. IMPLICATIONS FOR RESEARCH: Future research should focus on the development of personalized interventions to address attributes of problematic feeding such as sucking efficiency.

Monitoring oxygen saturation and heart rate during neonatal transition. comparison between two different pulse oximeters and electrocardiography.

OBJECTIVE: To compare the efficacy and reliability of two pulse-oximeters (POx) (Masimo Radical-7 and Nellcor™ Oxymax Bedside) and evaluate the feasibility of routine ECG monitoring during delivery room transition. STUDY DESIGN: Prospective observational comparative study. Sixty newborns were connected simultaneously to both POxs and ECG monitor (as a gold standard for HR). Times to achieve a stable signal were compared. Heart rates were compared to simultaneous ECG. RESULTS: A significant difference in times to stable signal was found: Mean, Median (Interquartile range) for Nellcor and Masimo, were 15, 8.5 (6-18) and 27, 12 (9-34) seconds, respectively. Compared to ECG, false bradycardia was displayed in 18 of 55 (35%) newborns by the Masimo POx and in no newborns by the Nellcor POx. Attaching the ECG monitor was feasible but consumed additional resources. CONCLUSIONS: The time for achievement of a stable saturation reading in an uncomplicated resuscitation setting differed significantly between POxs.

Do Neonatal Infections Require a Positive Blood Culture?

Neonatal sepsis is a major cause of worldwide morbidity and mortality. Blood cultures are considered the gold standard for diagnosis, but results are often delayed for 24 to 48 hours, and sensitivity, although improved by modern techniques, such as automated blood cultures, is variable and affected by the bacterial load. For these reasons, empiric antibiotics are frequently administered to avoid potential devastating consequences of untreated sepsis. Unnecessary antibiotic treatment has been associated with increased mortality and other adverse outcomes; therefore, antibiotics should be discontinued as soon as sepsis has been ruled out. Negative cultures pose a challenge to clinicians, who must distinguish between real sepsis and sepsis-like conditions (noninfectious or viral) which do not require antibiotics. Focal infections with negative blood cultures do require antibiotic treatment. Ultra-low bacteremia, primary or secondary to recent antibiotic exposure, is often associated with negative cultures, and some consider a short course of empiric antibiotics sufficient for clearing of bacteremia. Biomarkers and molecular methods based on polymerase chain reaction are important add-ons to clinical signs or symptoms for establishing the diagnosis of sepsis. Other promising future potential adjuvants are metabolomics. Antibiotic stewardship should be implemented to avoid or discontinue unnecessary treatment. Prevention of infection still remains the most important step for dealing with neonatal sepsis. KEY POINTS: · Blood cultures are the gold standard diagnosis of neonatal sepsis but sometimes may be negative.. · Other bacterial, viral, and noninfectious conditions may mimic sepsis, prompting initiation of empiric antibiotic treatments.. · Since a definition of neonatal sepsis is lacking, recognizing real septic episodes may be challenging..

Changing epidemiology and resistance patterns of pathogens causing neonatal bacteremia.

To conduct a survey of the local prevalent bacteria and antibiotic resistance in a referral tertiary neonatal intensive care unit (NICU), in order to assess the efficacy of local antibiotic policies. We reviewed all positive blood and cerebrospinal fluid cultures obtained between January 2007 and December 2017 in the NICU of Schneider Children's Medical Center of Israel. Early and late-onset bacteremia were defined as episodes occurring within or after the first 3 calendar days of life respectively. Empiric treatment included ampicillin and gentamicin or piperacillin-tazobactam and amikacin for early or late-onset bacteremia respectively. The prevalence and antibiotic resistance of the bacteria were described and compared over time. Eight hundred and twenty nine of 15,947 (5.2%) newborns had at least one episode of bacteremia; 81 had multiple episodes. The most common bacteria were Escherichia coli (32.35%) and group B Streptococcus (19.11%) or coagulase negative Staphylococcus (CoNS) (60.5%) and Klebsiella sp. (12.4%) in early or late-onset bacteremia respectively. Overall, all Gram-positive bacteria were susceptible to vancomycin and most non-CoNS to ampicillin. Nosocomial vs. vertical bacteremia had increased resistance to ampicillin and cephalosporins. Resistance of nosocomial bacteria to piperacillin-tazobactam was 22.4%, to amikacin 3.3%, and to meropenem 1.8%. Changes over time: Gram-negative bacteria had a significant increase in resistance to cotrimoxazole and piperacillin. The resistance to gentamicin doubled. Our empiric antibiotic regimen covers the most frequent isolates. Amikacin may replace gentamicin for selected sick patients in early-onset bacteremia. Piperacillin-tazobactam should be combined with amikacin until susceptibility is available.

Early neonatal hypoglycemia: incidence of and risk factors. A cohort study using universal point of care screening.

OBJECTIVE: The objective of this study is to determine the true incidence of early neonatal hypoglycemia and to confirm potential risk factors. STUDY DESIGN: The study was conducted at tertiary Medical Center in Israel, between June and September 2014. First blood glucose concentrations of all infants admitted to the nursery were measured using a "point of care" analyzer (Accu-Chek). We recorded risk factors for hypoglycemia such as birth weight, gestational age, maternal diabetes and demographics and analyzed their association with two hypoglycemia cutoffs: 40 and 47 mg/dl. RESULTS: Of 4000 newborns admitted during that period, 3595 were analyzed after excluding 405 who had missing data. Glucose level was obtained at a mean age of 74 ± 30 min. One hundred and twenty-four newborns (3.4%) had blood glucose levels below 40 mg/dl and 435 (12.1%) below 47 mg/dl. Univariate analyses revealed that gestational age, maternal diabetes, low birth weight (<2500 g), and twin delivery were associated with early neonatal hypoglycemia. Other risk factors (e.g. large or small for gestational age, birth weight >3800 g) were not. In multivariate analysis, gestational age remained the strongest association, while maternal diabetes and low birth weight became non-significant. CONCLUSIONS: We showed a high occurrence of early hypoglycemia in normal newborns using universal screening. The strongest risk factor was early gestational age. Surprisingly, incidence of early hypoglycemia in the presence of other classical risk factors was like that of the general population.

Effect of rewarming in oxygenation and respiratory condition after neonatal exposure to moderate therapeutic hypothermia.

BACKGROUND: To assess changes in clinical condition and oxygenation in neonates after rewarming following moderate therapeutic hypothermia (MTH) for neonatal encephalopathy. METHODS: Retrospective study of 28 neonates receiving MTH in a tertiary neonatal intensive care unit in Israel. We compared pre-and 24 h post-rewarming arterial oxygen saturation (SaO2) as measured by the blood gases analyzer, pulse-oximetry saturation (SpO2), and cardio-respiratory condition. RESULTS: The SpO2 declined from 96.9% (±2.9) before rewarming to 95.2% (±2.6) after rewarming (p < 0.001). Twelve neonates (42.9%) had clinical respiratory impairment (needing higher respiratory support or had new onset desaturations). In 16 neonates (57.1%) with no change in respiratory support after rewarming, SpO2 decreased from 98.3 ± 1.9% to 95.6 ± 3.0% (p < 0.001) and SaO2 decreased from 97.1 ± 1.7% to 96.0 ± 2.3% (p = 0.002). The mean SpO2 decrease was greater than mean SaO2 decrease (2.63 ± 1.8 and 1.1 ± 1.3 respectively, p = 0.021). CONCLUSION: Neonates who underwent MTH showed reduction in oxygenation after rewarming either by decreasing SpO2 or increasing FiO2 requirements. The SpO2 decline was larger than the SaO2 decline. We suggest careful monitoring of neonates after rewarming.

Normal Point of Care Glucose Values after Birth in the Well-Baby Nursery.

OBJECTIVE: Normal initial blood glucose values in healthy newborns are not well defined and are subject to controversy. Despite substantive research, there is no single initial value of glucose that can be used with certainty of safety in newborns, and thus various protocols and cutoffs have been proposed. STUDY DESIGN: We sought to characterize the normal values of blood glucose levels in a large cohort of neonates admitted to the well-baby nursery in Shaare Zedek Medical Center. The blood glucose levels were measured with a point of care (POC) glucometer (Accu-Chek Performa) within 180 minutes after birth. RESULTS: The study population included 3,912 newborns with a mean birth weight of 3,322 ± 439 g and a mean gestational age of 39.4 ± 1.3 weeks. Sampling was performed at a median age of 73 minutes (interquartile range [IQR], 55-92 minutes). Median glucose concentration was 58 (IQR, 51-67) mg/dL, and first, third, and fifth percentiles were 34, 39, and 41 mg/dL, respectively. CONCLUSION: Our data describe the normal range of POC blood glucose levels in healthy neonates on admission to the nursery. Extreme low levels were rare.

The effect of patent ductus arteriosus on pre-ductal and post-ductal perfusion index in preterm neonates.

OBJECTIVE: The ductus arteriosus is a blood vessel that connects the pulmonary artery to the descending aorta during fetal life and generally undergoes spontaneous closure shortly after birth. In premature neonates it often fails to close (patent ductus arteriosus-PDA), which can result in diversion of a significant part of the left-ventricular cardiac output to the pulmonary circulation. This left-to-right shunt may result in significant increase of pulmonary blood flow and decrease of systemic perfusion (hemodynamically significant PDA-hsPDA), which may lead to severe neonatal morbidity. The study objective was to find the relationship between hsPDA and perfusion index (PI), a photoplethysmographic parameter related to systemic perfusion. APPROACH: PI measures the relative systolic increase in tissue light absorption due to the systolic increase in the tissue blood volume. PI has been found to be directly related to tissue perfusion and is therefore expected to be affected by hsPDA. MAIN RESULTS: PI was found to be higher in preterm neonates with hsPDA after first week of life, in comparison to those with closed DA, despite the lower systemic perfusion, probably due to reverse flow during diastole. SIGNIFICANCE: In our study, perfusion index increased despite the lower systemic perfusion, indicating that in neonates with hsPDA, perfusion index is not necessarily a measure of perfusion. Nevertheless, PI can be used as a screening tool for suspicious PDA, in order to select a relatively small group of neonates for a more definitive examination by echocardiography, which is not suitable for universal screening.

Safety of fentanyl for peripherally inserted central catheter in non-intubated infants in the neonatal intensive care unit.

OBJECTIVE: To evaluate the safety of fentanyl in non-intubated infants undergoing peripherally inserted central catheter (PICC) placement. METHODS: A retrospective chart review of PICC placements over a 3 years' period. We compared the 12h periods before and after fentanyl for clinically significant cardiorespiratory events (spells). RESULTS: Of the 998 neonates screened, 258 were eligible. The mean standard deviation gestational age was 34.1 (4.3) weeks and the median (inter-quartile range) postnatal age was 4 (7, 11) days. The mean (standard deviation) fentanyl dose was 0.6 (0.2) µg/kg. Respiratory depression occurred only in two infants (prevalence rate = 0.78%, 95% CI (0, 1.85)). No cases of hypotension or chest wall rigidity occurred. There was no evidence of an increase in the number of infants with spells or in the number of spells per infant (p = 0.34 and p = 0.06, respectively). CONCLUSION: Fentanyl appears to be associated with only a small risk of respiratory depression in non-intubated infants.

Early application of the Ponseti casting technique for clubfoot correction in sick infants at the neonatal intensive care unit.

The treatment of congenital clubfoot has been changing rapidly since the mid-1990s with the worldwide use of the Ponseti method for serial casting and limited operative interventions. This method was first applied for isolated clubfeet and later on for other types of clubfoot (teratologic, residual, and neurogenic). Premature babies sustaining clubfoot commonly suffer from additional congenital and acquired medical problems. These may postpone clubfoot management until urgent issues are resolved. The current study describes early initiation of treatment of clubfoot in premature babies at the neonatal intensive care unit (NICU) and their outcomes. The study group included all babies diagnosed with clubfoot and managed in the NICU (for any etiology) between 2006 and 2012. Management was based on the Ponseti protocol for serial casting. We also report on neonates who died in the NICU before or during treatment. We specifically describe adverse events of early casting and situations necessitating removal of casts or termination of treatment. We diagnosed and treated 20 neonates with clubfoot (four females and 16 males, 10 bilateral cases). Gestational age ranged from 27 weeks to term. Eight were identified with clubfoot by prenatal sonographic survey and 10 were diagnosed with a defined syndrome. Seven had respiratory support, including one with a chest drain (50%). Length of stay in the NICU ranged from 3 to 90 days. Four neonates died while in the NICU (all syndromatic). In the remaining 16 cases, treatment began as early as medically possible. The first cast was applied within the first week of life in 14 cases. A total of 75 casts were applied during the study period. Three casts (4%) were removed because of leg edema or a need for venous access. Casts were routinely replaced every 4-7 days. Achilles tenotomies were performed in the NICU for babies achieving satisfactory correction. At last follow-up, 10 children were independent walkers and six were nonambulatory; all showed successful correction of clubfeet. The results of this study show that in most cases, clubfoot treatment is feasible and effective within the first week of life. Instances necessitating immediate cast removal are highlighted. Although while facing acute life-threatening medical problems, the treatment of clubfoot may not be considered a priority, most neonates will grow up into independent individuals; thus, every effort should be made to initiate the best clubfoot management with minimal delay.

Influence of hyperbilirubinemia on neonatal sucking.

BACKGROUND: Mothers of hyperbilirubinemic newborns frequently report to us that their infant is feeding poorly. As poor feeding in an extremely hyperbilirubinemic newborn may be an early sign of bilirubin encephalopathy, we hypothesized that neonatal hyperbilirubinemia would suppress the volume of feed ingested and diminish sucking parameters in comparison with minimally jaundiced neonates. OBJECTIVE: To determine whether hyperbilirubinemia does diminish feeding and sucking in neonates. STUDY DESIGN: Neonates in a well-baby nursery with serum total bilirubin (STB) ≥15.0mg/dL were compared with those with transcutaneous bilirubin ≤10mg/dL. Neonur, a modification of Krohn's Nutritive Sucking Apparatus, was used to quantify sucking parameters. Measurements during a 5min feeding period included volume ingested (measured manually), number of sucks, average maximum sucking pressure, number of bursts, average burst duration, pause between bursts duration, number of sucks per burst, and average intersuck interval. Outcome measures were volume ingested and, presuming decreased volume, sucking parameter analysis would determine the component affected by hyperbilirubinemia. RESULTS: 17 hyperbilirubinemic newborns (STB 17.8±1.6mg/dL) were compared with 24 controls, all with transcutaneous bilirubin <10.0mg/dL. The volume of feed ingested was similar between the hyperbilirubinemic newborns and controls (30.00 [20.00-42.50] ml vs. 25.00 [15.00-30.00] ml, p=0.2) (median [95% confidence interval]). No significant differences were noted in any of the other sucking parameters measured. CONCLUSIONS: At concentrations of STB in the range of 15-20mg/dL, hyperbilirubinemia did not diminish feed volume or sucking parameters in term newborns. Poor feeding in moderately hyperbilirubinemic newborns cannot be attributed to the level of bilirubin per se.

Diagnostic accuracy of capnography during high-frequency ventilation in neonatal intensive care units.

BACKGROUND AND OBJECTIVE: High-frequency ventilation (HFV) is a powerful tool for CO2 elimination, and thus requires careful monitoring of CO2 . Our aim was to assess the diagnostic accuracy (correlation, agreement, and trending) of continuous distal capnography (dCap) with PaCO2 in infants ventilated with HFV. DESIGN: This was a prospective, observational, multicenter study. dCap was compared with simultaneous PaCO2 ("gold standard") drawn from indwelling arterial line for patient care in term and preterm infants ventilated with HFV. dCap was obtained via the side-port of a double-lumen endotracheal-tube by a Microstream capnograph with specially designed software for HFV. RESULTS: Twenty-four infants participated in the study (median [range] gestational age [GA]: 26.8 [23.6-38.6] weeks). Analysis included 332 measurements. dCap was in correlation (r = 0.70, P < 0.001) but with less than adequate agreement (mean difference ± SD of the differences: -11.7 ± 10.3 mmHg) with PaCO2 . Comparable findings were found in the subgroup of infants <1,000 g (n = 240 measurements). Correlations were maintained in severe lung disease. Changes in dCap and in PaCO2 for consecutive measurements within each patient were correlated (r = 0.63, P < 0.001). Area under the receiver operating curves (ROC) for dCap to detect high (>60 mmHg) or low (<30 mmHg) PaCO2 was 0.83 (CI: 0.76-0.90) and 0.88 (CI: 0.79-0.97), respectively; P < 0.001. CONCLUSIONS: Our prospective study suggests that continuous dCap in infants ventilated with HFV may be helpful for trends and alarm for unsafe levels of PaCO2 . dCap is only a complimentary tool and cannot replace PaCO2 sampling because the agreement between these measurements was less than adequate.

Impact of Continuous Capnography in Ventilated Neonates: A Randomized, Multicenter Study.

OBJECTIVE: To compare the time spent within a predefined safe range of CO2 (30-60 mmHg) during conventional ventilation between infants who were monitored with distal end-tidal CO2 (dETCO2, or capnography) and those who were not. STUDY DESIGN: For this randomized, controlled multicenter study, ventilated infants with a double-lumen endotracheal tube were randomized to 1 of 2 groups: the open (monitored) group, in which data from the capnograph were recorded, displayed to the medical team, and used for patient care, and the masked group, in which data from the capnograph were recorded. However, the measurements were masked and not available for patient care. dETCO2 was compared with PaCO2 measurements recorded for patient care. RESULTS: Fifty-five infants (25 open, 30 masked) participated in the study (median gestational age, 28.6 weeks; range, 23.5-39.0 weeks). The 2 groups were comparable. dETCO2 was in good correlation (r = 0.73; P < .001) and adequate agreement (mean ± SD of the difference, 3.0 ± 8.5 mmHg) with PaCO2. Compared with infants in the masked group, those in the monitored group had significantly (P = .03) less time with an unsafe dETCO2 level (high: 3.8% vs 8.8% or low: 3.8% vs 8.9%). The prevalence of intraventricular hemorrhage or periventricular leukomalacia rate was lower in the monitored group (P = .02) and was significantly (P < .05) associated with the independent factors dETCO2 monitoring and gestational age. CONCLUSION: Continuous dETCO2 monitoring improved control of CO2 levels within a safe range during conventional ventilation in a neonatal intensive care unit. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01572272.