Effects of inhaled nitric oxide (iNO) in pulmonary hypertension secondary to arteriovenous malformations: a retrospective cohort study from the European iNO registry.

This study aims to assess the effects of inhaled nitric oxide (iNO) on oxygenation in the management of pulmonary hypertension (PH) secondary to arteriovenous malformations (AVMs) in neonates. This is a matched retrospective cohort study from January 1, 2013, to December 31, 2017. The European inhaled nitric oxide registry from 43 neonatal and pediatric ICUs in 13 countries across Europe was used to extract data. The target population was neonates treated with iNO for the management of PH. The cases (PH secondary to AVMs treated with iNO) were matched (1:4 ratio) to controls (PH without AVMs treated with iNO). The main outcome measure was the absolute change of oxygenation index (OI) from baseline to 60 min after starting iNO in cases and controls. The primary outcome of our study was that the mean absolute change in OI from baseline to after 60 min was higher among cases 10.7 (14), than in controls 6 (22.5), and was not statistically different between the groups. The secondary outcome variable - death before discharge - was found to be significantly higher in cases (55%) than in controls (8%). All the other variables for secondary outcome measures remained statistically insignificant.   Conclusion: Infants with PH secondary to AVMs treated with iNO did not respond differently compared to those presented with PH without AVMs treated with iNO. Right ventricular dysfunction on echocardiography was higher in cases than controls (cases: 66.7% and controls: 28.6%) but was not statistically significant. What is Known: • Arterioenous malformation (AVM) is a well-known cause of persistent pulmonary hypertension in newborns. Inhaled nitric oxide (iNO) is most commonly used as first-line therapy for pulmonary hypertension in newborns. • Around 40-50% of vein of Galen malformations (VOGMs) are found to have congestive heart failure in the neonatal period. What is New: • Neonates may present with an isolated PH of the newborn as the main feature of the VOGMs. A large proportion of cases with AVMs have been associated with right ventricular cardiac dysfunction.  • Results from one of the largest database registries in the world for iNO have been used to answer our research question.

Frequency and duration of extreme hypoxemic and hyperoxemic episodes during manual and automatic oxygen control in preterm infants: a retrospective cohort analysis from randomized studies.

OBJECTIVE: Neonatal exposure to episodic hypoxemia and hyperoxemia is highly relevant to outcomes. Our goal was to investigate the differences in the frequency and duration of extreme low and high SpO2 episodes between automated and manual inspired oxygen control. DESIGN: Post-hoc analysis of a cohort from prospective randomized cross-over studies. SETTING: Seven tertiary care neonatal intensive care units. PATIENTS: Fifty-eight very preterm neonates (32 or less weeks PMA) receiving respiratory support and supplemental oxygen participating in an automated versus manual oxygen control cross-over trial. MAIN MEASURES: Extreme hypoxemia was defined as a SpO2 < 80%, extreme hyperoxemia as a SpO2 > 98%. Episode duration was categorized as < 5 seconds, between 5 to < 30 seconds, 30 to < 60 seconds, 60 to < 120 seconds, and 120 seconds or longer. RESULTS: The infants were of a median postmenstrual age of 29 (28-31) weeks, receiving a median FiO2 of 0.28 (0.25-0.32) with mostly receiving non-invasive respiratory support (83%). While most of the episodes were less than 30 seconds, longer episodes had a marked effect on total time exposure to extremes. The time differences in each of the three longest durations episodes (30, 60, and 120 seconds) were significantly less during automated than during manual control (p < 0.001). Nearly two-third of the reduction of total time spent at the extremes between automated and manual control (3.8 to 2.1% for < 80% SpO2 and 3.0 to 1.6% for > 98% SpO2) was seen in the episodes of at least 60 seconds. CONCLUSIONS: This study shows that the majority of episodes preterm infants spent in SpO2 extremes are of short duration regardless of manual or automated control. However, the infrequent longer episodes not only contribute the most to the total exposure, but also their reduction in frequency to the improvement associated with automated control.

Inhaled nitric oxide (iNO) for preventing prematurity-related bronchopulmonary dysplasia (BPD): 7-year follow-up of the European Union Nitric Oxide (EUNO) trial.

OBJECTIVES: Most studies of inhaled nitric oxide (iNO) for prevention of bronchopulmonary dysplasia (BPD) in premature infants have focused on short-term mortality and morbidity. Our aim was to determine the long-term effects of iNO. METHODS: A 7-year follow-up was undertaken of infants entered into a multicenter, double-blind, randomized, placebo-controlled trial of iNO for prevention of BPD in premature infants born between 24 and 28 weeks plus six days of gestation. At 7 years, survival and hospital admissions since the 2-year follow-up, home oxygen therapy in the past year, therapies used in the previous month and growth assessments were determined. Questionnaires were used to compare general health, well-being, and quality of life. RESULTS: A total of 305 children were assessed. No deaths were reported. Rates of hospitalization for respiratory problems (6.6 vs. 10.5%, iNO and placebo group, respectively) and use of respiratory medications (6.6 vs. 9.2%) were similar. Two patients who received iNO and one who received placebo had received home oxygen therapy. There were no significant differences in any questionnaire-documented health outcomes. CONCLUSIONS: iNO for prevention of BPD in very premature infants with respiratory distress did not result in long-term benefits or adverse long-term sequelae. In the light of current evidence, routine use of iNO cannot be recommended for prevention of BPD in preterm infants.

Automated versus Manual Oxygen Control with Different Saturation Targets and Modes of Respiratory Support in Preterm Infants.

OBJECTIVE: To determine the efficacy and safety of automated adjustment of the fraction of inspired oxygen (FiO2) in maintaining arterial oxygen saturation (SpO2) within a higher (91%-95%) and a lower (89%-93%) target range in preterm infants. STUDY DESIGN: Eighty preterm infants (gestational age [median]: 26 weeks, age [median] 18 days) on noninvasive (n = 50) and invasive (n = 30) respiratory support with supplemental oxygen, were first randomized to one of the SpO2 target ranges and then treated with automated FiO2 (A-FiO2) and manual FiO2 (M-FiO2) oxygen control for 24 hours each, in random sequence. RESULTS: The percent time within the target range was higher during A-FiO2 compared with M-FiO2 control. This effect was more pronounced in the lower SpO2 target range (62 ± 17% vs 54 ± 16%, P < .001) than in the higher SpO2 target range (62 ± 17% vs 58 ± 15%, P < .001). The percent time spent below the target or in hypoxemia (SpO2 <80%) was consistently reduced during A-FiO2, independent of the target range. The time spent above the target range or at extreme hyperoxemia (SpO2 >98%) was only reduced during A-FiO2 when targeting the lower SpO2 range (89%-93%). These outcomes did not differ between infants on noninvasive and invasive respiratory support. Manual adjustments were significantly reduced during A-FiO2 control. CONCLUSIONS: A-FiO2 control improved SpO2 targeting across different SpO2 ranges and reduced hypoxemia in preterm infants on noninvasive and invasive respiratory support. TRIAL REGISTRATION: ISRCTN 56626482.

Effects of a sustained inflation in preterm infants at birth.

OBJECTIVE: To assess the clinical effect of an initial sustained inflation of 10 seconds and 25 cmH2O in preterm infants at birth. STUDY DESIGN: In this observational study inflation pressures and tidal volumes were recorded with the use of respiratory function monitoring of preterm infants <32 weeks' gestation receiving a sustained inflation. Inspiratory tidal volume (Vti) and expiratory tidal volume (Vte) of sustained inflation and cumulative Vti and Vte of breaths during sustained inflation were determined. Heart rate and oxygen saturation were measured before and after the sustained inflation. RESULTS: Seventy infants were included (median [IQR]: gestational age 29 [27-30] weeks). Mean (SD) sustained inflation duration was 10.5 seconds (2.9 seconds) with positive inflation pressure 24.2 cmH2O (2.3 cmH2O) and positive end-expiratory pressure 6.0 cmH2O (1.8 cmH2O). In 20 of 70 infants, no volumes were delivered during the sustained inflation because of mask leak. No leak occurred in 50 of 70 infants, of whom 36 of 50 breathed during the sustained inflation. In 14 of the infants who did not breathe, Vti and Vte were 0.9 mL/kg (0.4-2.7 mL/kg) and 0.6 mL/kg (0.1-2.0 mL/kg) with a functional residual capacity (FRC) gain of 0.0 (-0.5 to 0.6) mL/kg. In 36 of 50 infants who breathed during the sustained inflation, Vti was 2.9 mL/kg (0.9-9.2 mL/kg) and Vte 3.8 mL/kg (1.0-5.9 mL/kg), whereas cumulative Vti of breaths was 16.4 mL/kg (6.8-23.3 mL/kg) and cumulative Vte of breaths was 5.8 mL/kg (1.2-16.8 mL/kg) with an FRC gain of 7.1 mL/kg (1.7-15.9 mL/kg). Heart rate and oxygen saturation did not increase immediately after the sustained inflation. CONCLUSIONS: A sustained inflation of 10 seconds and 25 cmH2O in preterm infants at birth was not effective unless infants breathed. Although large mask leak accounted for approximately one-third of failures, as FRC gain was only associated with breathing, we speculate that active glottic adduction may be responsible for most failures.

Effective ventilation and chest compressions during neonatal resuscitation - the role of the respiratory device.

BACKGROUND: The success of cardiopulmonary resuscitation (CPR) in newborns largely depends on effective lung ventilation; however, a direct randomized comparison using different available devices has not yet been performed. METHODS: Thirty-six professionals were exposed to a realistic newborn CPR scenario. Ventilation with either a bag-valve mask (BVM), T-piece, or ventilator was applied in a randomized manner during CPR using a Laerdal manikin. The primary outcome was the number of unimpaired inflations, defined as the peak of the inflation occurring after chest compression and lasting at least 0.35 s before the following chest compression takes place. The secondary outcomes were tidal volume delivered and heart compression rate. To simulate potential distractions, the entire scenario was performed with or without a quiz. Statistically, a mixed model assessing fixed effects for experience, profession, device, and distraction was used to analyze the data. For direct comparison, one-way ANOVA with Bonferroni's correction was applied. RESULTS: The number of unimpaired inflations was highest in health care professionals using the BVM with a mean ± standard deviation of 12.8 ± 2.8 (target: 15 within 30 s). However, the tidal volumes were too large in this group with a tidal volume of 42.5 ± 10.9 ml (target: 25-30 ml). The number of unimpaired breaths with the mechanical ventilator and the T-piece system were 11.6 (±3.6) and 10.1 (±3.7), respectively. Distraction did not change these outcomes, except for the significantly lower tidal volumes with the T-piece during the quiz. CONCLUSIONS: In summary, for our health care professionals, ventilation using the mechanical ventilator seemed to provide the best approach during CPR, especially in a population of preterm infants prone to volutrauma.

Comparison of Cardiac Output Measurement by Electrical Velocimetry with Echocardiography in Extremely Low Birth Weight Neonates.

INTRODUCTION: Electrical velocimetry (EV) offers a noninvasive tool for continuous cardiac output (CO) measurements which might facilitate hemodynamic monitoring and targeted therapy in low birth neonates, in whom other methods of CO measurement are not practicably feasible. METHODS: This prospective observational study compared simultaneous cardiac output measurements by electrical velocimetry (COEV) with transthoracic echocardiography (COTTE) in extremely low birth weight (ELBW) neonates in the neonatal intensive care unit (NICU). Echocardiography was performed by 1 single examiner. Data were analyzed by Bland-Altman analysis and independent-samples analysis of variance. A mean percentage error (MPE) of <30% and limits of agreement (LOA) up to ±30% were considered clinically acceptable. RESULTS: Thirty-eight ELBW neonates were studied and yielded 85 pairs of COEV and COTTE measurements. Bland-Altman analysis showed an overall bias (the mean difference) and LOA of -126 and -305 to +52 mL min-1, respectively, and an MPE of 66%. Patients with patent ductus arteriosus had a higher bias with LOA and MPE of -166.8, -370.7 to +37 mL min-1, and 69%, respectively. The overall true precision was 58%. CONCLUSION: This study showed high bias and lack of agreement between EV and TTE for measurement of CO in ELBW infants in NICU, limiting applicability of EV to monitor absolute values.

Cerebral Oxygenation in Preterm Infants Developing Cerebral Lesions.

Background: We investigated the association between cerebral tissue oxygen saturation (cStO2) measured by near-infrared spectroscopy (NIRS) and cerebral lesions including intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL). Methods: Preterm infants <1,500 g received continuous cStO2 monitoring, initiated at the earliest time possible and recorded until 72 h of life. Mean cStO2 over periods of 5, 15, 30 min and 1 h were calculated. To calculate the burden of cerebral hypoxia, we defined a moving threshold based on the 10th percentile of cStO2 of healthy study participants and calculated the area under the threshold (AUT). cStO2 <60% for >5 min was regarded a critical event. The study was registered on clinicaltrials.gov (ID NCT01430728, URL: https://clinicaltrials.gov/ct2/show/NCT01430728?id=NCT01430728&draw=2&rank=1). Results: Of 162 infants (gestational age: mean 27.2 weeks, standard deviation 20 days; birth weight: mean 852 g, standard deviation 312 g) recorded, 24/12 (14.8%/7.4) developed any/severe IVH/PVL. Mean cStO2 was significantly lower in infants with IVH/PVL as well as severe IVH/PVL. In addition, we observed critical events defined by mean cStO2 over 5 min <60% in four infants with severe IVH/PVL during NIRS monitoring. AUT showed no statistically significant difference between outcome groups. Conclusion: These findings suggest that cStO2 is lower in infants developing IVH/PVL. This may be related to lower oxygenation and/or perfusion and implies that cStO2 could potentially serve as an indicator of imminent cerebral lesions.

Cerebral oxygenation in very low birth weight infants supported with sustained lung inflations after birth.

Sustained lung inflations (SIs) immediately after birth might decrease the need for subsequent mechanical ventilation in preterm infants. However, effects of SIs on oxygenation and hemodynamics are undetermined. Our aim was to study immediate effects of SIs on heart rate, arterial oxygen saturation, and cerebral tissue oxygen saturation in preterm infants supported with SIs after birth for lung recruitment. Heart rate, arterial oxygen saturation, and cerebral tissue oxygen saturation using near infrared spectroscopy was measured in 24 preterm infants of 28.0 (26.6-29.3) wk GA [median (interquartile range)] during resuscitation using up to three SIs of 20, 25, and 30 cm H2O of 15 s duration each followed by nasal continuous positive airway pressure (CPAP) as first line approach for respiratory support. During positioning and suctioning immediately after delivery infants became progressively hypoxemic and bradycardic before respiratory support was initiated. In 18 infants (75%), more than one SI were applied. During the last SIs, there was a rapid increase in the infants' heart rate and an increase in cerebral tissue oxygen saturation. Arterial saturation increased with slight delay. In conclusion, effective last sustained inflations increase heart rate and cerebral tissue oxygen saturation to be followed by an increase in arterial saturation.

"Current concepts in assisted mechanical ventilation in the neonate" - Part 2: Understanding various modes of mechanical ventilation and recommendations for individualized disease-based approach in neonates.

Mechanical ventilation is a lifesaving intervention in critically ill preterm and term neonates. However, it has the potential to cause significant damage to the lungs resulting in long-term complications. Understanding the pathophysiological process and having a good grasp of the basic concepts of conventional and high-frequency ventilation is essential for any medical or allied healthcare practitioner involved in the neonates' respiratory management. This review aims to describe the various types and modes of ventilation usually available in neonatal units. It also describes recommendations of an individualized disease-based approach to mechanical ventilation strategies implemented in the authors' institutions.

"Current concepts of mechanical ventilation in neonates" - Part 1: Basics.

Mechanical ventilation is potentially live saving in neonatal patients with respiratory failure. The main purpose of mechanical ventilation is to ensure adequate gas exchange, including delivery of adequate oxygenation and enough ventilation for excretion of CO2. The possibility to measure and deliver small flows and tidal volumes have allowed to develop very sophisticated modes of assisted mechanical ventilation for the most immature neonates, such as volume targeted ventilation, which is used more and more by many clinicians. Use of mechanical ventilation requires a basic understanding of respiratory physiology and pathophysiology of the disease leading to respiratory failure. Understanding pulmonary mechanics, elastic and resistive forces (compliance and resistance), and its influence on the inspiratory and expiratory time constant, and the mechanisms of gas exchange are necessary to choose the best mode of ventilation and adequate ventilator settings to minimize lung injury. Considering the pathophysiology of the disease allows a physiology-based approach and application of these concepts in daily practice for decision making regarding the use of modes and settings of mechanical ventilation, with the ultimate aim of providing adequate gas exchange and minimising lung injury.

Transthoracic Echocardiography of the Neonatal Laboratory Piglet.

Background: Newborn piglets are commonly used in biomedical research. However, cardiovascular imaging of this species is quite challenging. For point of care diagnostics of heart function transthoracic echocardiography may be used, which appears to differ comparing newborn piglets with adult pigs. To date, there are few data or studies on the feasibility and quality of measurement of functional echocardiographic parameters in very small neonatal piglets. Objectives: To study the feasibility of transthoracic echocardiography in very small newborn piglets in supine position. Methods: In 44 anesthetized and intubated newborn piglets, positioned in supine position [age 32 h (12-44 h), weight 1,220 g (1,060-1,495 g), median (IQR)] transthoracic echocardiography was performed using a point of care ultrasound device (M-Turbo©, FujiFilm SonoSite BV, Amsterdam, Netherlands), and a standard ultrasound transducer. Results: Using 2D- and M-mode-imaging left- and right-sided heart structures were accessible to transthoracic echocardiography in neonatal piglets. Diameters of the interventricular septum, the left ventricle, and the posterior wall were measured and ejection fraction and shortening fraction was calculated. Both left and right ventricular outflow tract could be imaged, and ventricular filling and systolic function could be evaluated. Furthermore, we were able to assess shunts of fetal circulation, such as patent ductus arteriosus, structure of the heart valves and congenital heart defects including ventricular septal defect. Conclusions: In summary, transthoracic echocardiography is feasible for assessment of cardiovascular function even in very small newborn laboratory piglets in supine position.

Predictive Value of Thompson-Score for Long-Term Neurological and Cognitive Outcome in Term Newborns with Perinatal Asphyxia and Hypoxic-Ischemic Encephalopathy Undergoing Controlled Hypothermia Treatment.

BACKGROUND: The so-called Thompson-score (TS) for newborns with hypoxic-ischemic encephalopathy (HIE) was developed before the introduction of controlled hypothermia as clinical routine. Information on the predictive value of TS in newborns undergoing therapeutic hypothermia to estimate long-term outcome is limited. OBJECTIVES: To determine the predictive value of TS to estimate long-term cognitive and neurological outcome in newborns with perinatal asphyxia treated with controlled hypothermia. METHODS: Thirty-six term newborns with HIE undergoing controlled hypothermia were followed using Wechsler Preschool and Primary Scale of intelligence III test and standardized neurological examination. The primary outcome was survival without cognitive impairment, defined as an IQ ≥85. Secondary outcomes were motor outcomes, survival without relevant neurological impairment, death and epilepsy. RESULTS: Follow-up was done in 33 out of 36 (91.6%) infants at 53 ± 12 months (mean ± SD). For all investigated parameters, a statistically significant relationship with peak TS was demonstrated. A one-point increase in peak TS indicated an OR (95% CI) of 1.5 (1.1-2.0, p = 0.006) for death or cognitive impairment, an OR (95% CI) of 2.2 (1.3-3.8, p = 0.004) for death or relevant neurologic impairment, an OR (95% CI) of 2.1 (1.3-3.5, p = 0.005) for death or epilepsy and an OR (95% CI) of 1.5 (1.1-2.1, p = 0.02) for death. Although the TS for newborns with adverse outcome (death or cognitive impairment) compared to normal outcome tended to be higher (13 [4-16] vs. 9 [0-13], d1; 15 [5-19] vs. 9 [1-14], d2; 14 [5-21] vs. 8 [2-15], d3; median [range]), there was a considerable overlap during the first 3 days of life between both groups. CONCLUSIONS: The TS seems to be a prognostic tool for predicting the long-term outcome in asphyxiated term newborns undergoing controlled hypothermia after the third day of life. A higher score appears to be significantly associated with an adverse outcome.

Successful Resuscitation in a Model of Asphyxia and Hemorrhage to Test Different Volume Resuscitation Strategies. A Study in Newborn Piglets After Transition.

Background: Evidence for recommendations on the use of volume expansion during cardiopulmonary resuscitation in newborn infants is limited. Objectives: To develop a newborn piglet model with asphyxia, hemorrhage, and cardiac arrest to test different volume resuscitation on return of spontaneous circulation (ROSC). We hypothesized that immediate red cell transfusion reduces time to ROSC as compared to the use of an isotonic crystalloid fluid. Methods: Forty-four anaesthetized and intubated newborn piglets [age 32 h (12-44 h), weight 1,220 g (1,060-1,495g), Median (IQR)] were exposed to hypoxia and blood loss until asystole occurred. At this point they were randomized into two groups: (1) Crystalloid group: receiving isotonic sodium chloride (n = 22). (2) Early transfusion group: receiving blood transfusion (n = 22). In all other ways the piglets were resuscitated according to ILCOR 2015 guidelines [including respiratory support, chest compressions (CC) and epinephrine use]. One hour after ROSC piglets from the crystalloid group were randomized in two sub-groups: late blood transfusion and infusion of isotonic sodium chloride to investigate the effects of a late transfusion on hemodynamic parameters. Results: All animals achieved ROSC. Comparing the crystalloid to early blood transfusion group blood loss was 30.7 ml/kg (22.3-39.6 ml/kg) vs. 34.6 ml/kg (25.2-44.7 ml/kg), Median (IQR). Eleven subjects did not receive volume expansion as ROSC occurred rapidly. Thirty-three animals received volume expansion (16 vs. 17 in the crystalloid vs. early transfusion group). 14.1% vs. 10.5% of previously extracted blood volume in the crystalloid vs. early transfusion group was infused before ROSC. There was no significant difference in time to ROSC between groups [crystalloid group: 164 s (129-198 s), early transfusion group: 163 s (162-199 s), Median (IQR)] with no difference in epinephrine use. Conclusions: Early blood transfusion compared to crystalloid did not reduce time to ROSC, although our model included only a moderate degree of hemorrhage and ROSC occurred early in 11 subjects before any volume resuscitation occurred.

Influence of PCO2 Control on Clinical and Neurodevelopmental Outcomes of Extremely Low Birth Weight Infants.

BACKGROUND: Levels or fluctuations in the partial pressure of CO2 (PCO2) may affect outcomes for extremely low birth weight infants. OBJECTIVES: In an exploratory analysis of a randomized trial, we hypothesized that the PCO2 values achieved could be related to significant outcomes. METHODS: On each treatment day, infants were divided into 4 groups: relative hypocapnia, normocapnia, hypercapnia, or fluctuating PCO2. Ultimate assignment to a group for the purpose of this analysis was made according to the group in which an infant spent the most days. Statistical analyses were performed with analysis of variance (ANOVA), the Kruskal-Wallis test, the χ2 test, and the Fisher exact test as well as by multiple logistic regression. RESULTS: Of the 359 infants, 57 were classified as hypocapnic, 230 as normocapnic, 70 as hypercapnic, and 2 as fluctuating PCO2. Hypercapnic infants had a higher average product of mean airway pressure and fraction of inspired oxygen (MAP × FiO2). For this group, mortality was higher, as was the likelihood of having moderate/severe bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and poorer neurodevelopment. Multiple logistic regression analyses showed an increased risk for BPD or death associated with birth weight (p < 0.001) and MAP × FiO2 (p < 0.01). The incidence of adverse neurodevelopment was associated with birth weight (p < 0.001) and intraventricular hemorrhage (IVH; p < 0.01). CONCLUSIONS: Birth weight and respiratory morbidity, as measured by MAP × FiO2, were the most predictive of death or BPD and NEC, whereas poor neurodevelopmental outcome was associated with low birth weight and IVH. Univariate models also identified PCO2. Thus, hypercapnia seems to reflect greater disease severity, a likely contributor to differences in outcomes.

Cerebral oxygenation and desaturations in preterm infants - a longitudinal data analysis.

OBJECTIVE: Hypoxemic episodes commonly occur in very preterm infants and may be associated with several adverse effects. Cerebral tissue oxygen saturation (StO2) as measured by near infrared spectroscopy (NIRS) may be a useful measure to assess brain oxygenation. However, knowledge on variability of StO2 is limited in preterm infants at this time, so StO2 dependency on arterial oxygenation (SpO2) and heart rate (HR) was assessed in preterm infants using statistical methods of time series analysis. STUDY DESIGN: StO2, SpO2, and HR were recorded from 15 preterm infants every 2 seconds for six hours. Statistical methods of time series and longitudinal data analysis were applied to the data. RESULT: The mean StO2 level was found as 72% (95% confidence interval (CI) 55.5% -85.5%) based on a moving average process with a 5 minute order. Accordingly, longitudinal SpO2 measurements showed a mean level of 91% (95% CI 69% -98%). Generally, compensation strategies to cope with both StO2 and SpO2 desaturations were observed in the studied patients. SpO2 had a significant effect on cerebral oxygenation (p < 0.001), but HR did not, which led to inconclusive results considering different time intervals. CONCLUSION: In infants with intermittent hypoxemia and bradycardia, we found a mean StO2 level of 72% and a strong correlation with SpO2. We observed large differences between individuals in the ability to maintain StO2 at a stable level.

Tidal Volume Delivery and Endotracheal Tube Leak during Cardiopulmonary Resuscitation in Intubated Newborn Piglets with Hypoxic Cardiac Arrest Exposed to Different Modes of Ventilatory Support.

BACKGROUND: There are few data available on the interaction of inflations, chest compressions (CC), and delivery of tidal volumes in newborn infants undergoing resuscitation in the presence of endotracheal tube (ET) leaks. OBJECTIVES: To determine the effects of different respiratory support strategies along with CC on changes in tidal volume and ET leaks in hypoxic newborn piglets with cardiac arrest. METHODS: Asphyxiated newborn piglets, intubated with weight-adapted uncuffed ET, were randomized into three groups and resuscitated according to ILCOR 2010 guidelines: (1) T-piece resuscitator (TPR) group = peak inspiratory pressure (PIP)/positive end-expiratory pressure (PEEP) 25/5 cm H2O, rate 30/min, inflations interposed between CC (3:1 ratio); (2) self- inflating bag (SIB) group = PIP 25 cm H2O without PEEP, rate 30/min, inflations interposed between CC (3:1 ratio), and (3) ventilator group = PIP/PEEP of 25/5 cm H2O, rate 30/min. CC were applied with a rate of 120/min without synchrony to inflations. RESULTS: We observed a significant increase of leak (average increase 11.4%) when CC was added to respiratory support (p = 0.0001). Expired tidal volume was larger in the SIB group than in the two other modes which both applied PEEP. However, tidal volumes caused by CC only were larger in the two groups with PEEP than in the SIB group (without PEEP). CONCLUSIONS: There is interaction between lung inflations and CC affecting leak and delivery of tidal volume, which may be influenced by the mode/device used for respiratory support. Leak is larger in the presence of PEEP. However, CC cause additional tidal volume which is larger in the presence of PEEP.

Reliability of Pulse Oximetry during Progressive Hypoxia, Cardiopulmonary Resuscitation, and Recovery in a Piglet Model of Neonatal Hypoxic Cardiac Arrest.

BACKGROUND: Pulse oximetry is widely used in intensive care and emergency conditions to monitor arterial oxygenation and to guide oxygen therapy. OBJECTIVE: To study the reliability of pulse oximetry in comparison with CO-oximetry in newborn piglets during progressive hypoxia, cardiac arrest, cardiopulmonary resuscitation (CPR), and after return of spontaneous circulation (ROSC). METHODS: Thirty-three newborn piglets were exposed to hypoxia until asystole occurred and then resuscitated until ROSC. Arterial oxygen saturation was monitored continuously by pulse oximetry (SpO2) with one sensor applied to the wrist of the right forelimb (FL) and another to the thigh of the left hind limb (HL). Arterial functional oxygen saturation (SaO2) was measured at baseline and at predefined intervals during each phase of the experiment. SpO2 was compared with coinciding SaO2 values and bias considered whenever the difference (SpO2 - SaO2) was beyond ±5%. RESULTS: Bias values were lower at the baseline measurements (-3.7 ± 2.3% in FL and -4.1 ± 3.4% in HL) as well as after ROSC (1.5 ± 4.2% in FL and 0.2 ± 4.6% in HL) with higher precision and accuracy than during other experiment phases. During hypoxia induction, cardiac arrest, and CPR, there was a marked decrease in precision and accuracy as well as an increase in bias up to 43 ± 26 and 56 ± 27% in FL and HL, respectively, over a range of SaO2 from 13 to 51%. CONCLUSION: Pulse oximetry showed increased bias and decreased accuracy and precision during marked hypoxemia in a model of neonatal hypoxic cardiac arrest.

Permissive hypercapnia for severe acute respiratory distress syndrome in immunocompromised children: A single center experience.

BACKGROUND: Controlled hypoventilation while accepting hypercapnia has been advocated to reduce ventilator-induced lung injury. The aim of the study was to analyze outcomes of a cohort of immunocompromised children with acute respiratory distress syndrome (ARDS) ventilated with a strategy of stepwise increasing PCO2 targets up to 140 mm Hg. METHODS: Retrospective analysis of outcomes of a cohort of children with oncologic disease or after stem cell transplantation and severe respiratory failure in comparison with a historical control cohort. RESULTS: Out of 150 episodes of admission to the PICU 88 children underwent invasive mechanical ventilation for >24h (overall survival 75%). In a subgroup of 38 children with high ventilator requirements the PCO2 target ranges were increased stepwise. Fifteen children survived and were discharged from the PICU. Severe pulmonary hypertension was seen in two patients and no case of cerebral edema was observed. Long term outcome was available in 15 patients and 10 of these patients survived without adverse neurological sequelae. With introduction of this strategy survival of immunocompromised children undergoing mechanical ventilation for >24h increased to 48% compared to 32% prior to introduction (historical cohort). CONCLUSIONS: A ventilation strategy incorporating very high carbon dioxide levels to allow for low tidal volumes and limited inspiratory pressures is feasible in children. Even severe hypercapnia may be well tolerated. No severe side effects associated with hypercapnia were observed. This strategy could potentially increase survival in immunocompromised children with severe ARDS.