The Cause of Acute Respiratory Failure Predicts the Outcome of Noninvasive Ventilation in Immunocompromised Children.

BACKGROUND: Noninvasive ventilation (NIV) may be superior to conventional therapy in immunocompromised children with respiratory failure. METHODS: Mortality, success rate, prognostic factors and side effects of NIV for acute respiratory failure (ARF) were investigated retrospectively in 41 in children with primary immunodeficiency, after stem cell transplantation or chemotherapy for oncologic disease. RESULTS: In 11/41 (27%) children invasive ventilation was avoided and patients were discharged from ICU. In children with NIV failure ICU-mortality was 19/30 (63%). 8/11 (72%) children with NIV success had recurrence of ARF after 27 days. Only 4/11 (36%) children with first episode NIV success and 8/30 (27%) with NIV failure survived to hospital discharge. Lower FiO2, SpO2/FiO2 and blood culture positive bacterial sepsis were predictive for NIV success, while fungal sepsis or culture negative ARF were predictive for NIV failure. We observed catecholamine treatment in 14/41 (34%), pneumothorax in 2/41 (5%), mediastinal emphysema in 3/41 (7%), a life threatening nasopharyngeal hemorrhage and need for resuscitation during intubation in 5/41 (12%) NIV-episodes. CONCLUSIONS: The prognosis of ARF in immunocompromised children remains guarded independent of initial success or failure of NIV due to a high rate of recurrent ARF. Reversible causes like bacterial sepsis had a higher NIV response rate. Relevant side effects of NIV were observed.

[Mortality of extremely low birthweight infants - large differences between quality assurance data and the national birth/death registry]. / Mortalität sehr unreifer Frühgeborener - Erhebliche Diskrepanz zwischen Neonatalerhebung und amtlicher Geburten-/Sterbestatistik.

BACKGROUND: To evaluate neonatal outcome, the German neonatal quality assurance dataset is often used. However, a systematic bias may occur, as not all live births are registered in this dataset. The aim of our study was to evaluate the magnitude of this systematic error by comparing this dataset to the national birth/death registry. METHODS: The summary statistics of live births and deaths with a birthweight <1 500 g from the quality assurance datasets 2007-2009 of 5 German States (Baden-Württemberg, Bavaria, Hesse, Lower-Saxony and North Rhine-Westfalia) were compared with the dataset from the national birth/death registry. RESULTS: Our analysis included 68% of the German birth cohort 2007-2009. The quality assurance dataset included 1 151 of 1 716 neonatal deaths (67.1%) in infants with a birthweight <1,000 g registered within the national birth/death registry; 565 deaths were missing. A total of 277 of 303 deaths (94.1%) with a birthweight 1,000-1,499 g were registered; 26 deaths were missing. In the state of Baden-Württemberg up to 11% more infants were registered in the quality assurance dataset than in the national registry, but an average of 36 neonatal deaths/year with a birthweight <1,000 g were missing (63.4% registration rate). CONCLUSION: This analysis shows that the quality assurance data miss more than 1/3 of deaths in extremely low birthweight infants. Transfers between hospitals may result in multiple data entries and additional bias. Comparing outcome statistics based on the neonatal quality assurance dataset may lead to a substantial systematic error. Linkage to national birth and death certificates and/or to the perinatal dataset is urgently needed.

Neonatal fellowship. Neonatal pneumopericardium: successful treatment with nitrogen washout technique.

Pneumopericardium in the neonate is a rare event but is associated with significant morbidity and mortality. We describe a neonate with mild respiratory distress and cardiovascular compromise after delivery and resuscitation. A large isolated pneumopericardium was diagnosed. Treatment with an oxygen hood (FiO2 1.00) resulted in a complete resolution of the pneumopericardium within 12 hours.

Effects of short sustained lung inflations on cerebral blood flow and cerebral tissue oxygenation in the juvenile rabbit.

BACKGROUND: Sustained lung inflations improve oxygenation but may impair hemodynamics. This study aimed to determine effects of short sustained inflations on cerebral blood flow and cerebral tissue oxygenation in experimental lung injury. METHODS: Experiments were performed in 6 juvenile ventilated New Zealand white rabbits. The effects of a series of sustained inflations at 20, 25 and 30 cmH2O pressure for 15 seconds duration each on hemodynamics, cerebral blood flow and cerebral tissue oxygenation were determined by laser Doppler flowmetry and cerebral tissue oxygen tension measurement in naive animals, after surfactant depletion and subsequent fluid filling of the lung. RESULTS: During the series of sustained inflations the mean arterial blood pressure decreased by 73%, 52% and 32% and the mean cerebral blood flow decreased by 73%, 39% and 30% in naive animals, after surfactant depletion and with fluid filling of the lung respectively. Arterial oxygen saturation was maintained or increased, while mean cerebral tissue oxygenation decreased by 48% (naive), 8% (surfactant depletion) or increased by 81% (surfactant depletion and fluid filling). Three minutes after the sustained inflations blood gases were similar to the blood gases prior to the sustained inflations. CONCLUSION: A series of short sustained lung inflations of 15 seconds duration can impair cerebral blood flow but increase arterial oxygen saturation in this juvenile animal model. The combination of these effects resulted in either a decrease or increase in regional cerebral tissue oxygenation.

Brain oxygenation monitoring during neonatal resuscitation of very low birth weight infants.

OBJECTIVE: To explore if regional cerebral tissue oxygen saturation monitoring by near-infrared spectroscopy (NIRS) is feasible during neonatal resuscitation of very low birth weight (VLBW) infants after birth. STUDY DESIGN: Cerebral tissue oxygen saturation was measured by NIRS in 51 VLBW infants (mean gestational age: 27.8 weeks) during the first 10 min after delivery. RESULT: A regional cerebral tissue oxygen saturation signal was available after a median (interquartile range) age of 52 (44 to 68) s. In three infants the signal was obtained after 10 min of age. After delivery cerebral tissue oxygen saturation rose continuously from 37 (31 to 49) % at 1 minute of age and reached a steady state in the range of 61 to 84% ∼7 min after birth. Percentiles of cerebral tissue oxygen saturation of this cohort of preterm infants are given. CONCLUSION: Cerebral tissue oxygen saturation monitoring is feasible during neonatal resuscitation of VLBW infants within the first minutes of life.

Predictors of early nasal CPAP failure and effects of various intubation criteria on the rate of mechanical ventilation in preterm infants of <29 weeks gestational age.

INTRODUCTION: Delivery room management using early nasal continuous positive airway pressure (nCPAP) may delay surfactant therapy. OBJECTIVE: To identify factors associated with early nCPAP failure and effects of various intubation criteria on rate and time of intubation. DESIGN: Retrospective analysis of the first 48 h in infants of 23-28 weeks gestational age (GA) treated with sustained inflations followed by early nCPAP. RESULTS: Of 225 infants (GA 26.2±1.6 weeks) 140 (62%) could be stabilised with nCPAP in the delivery room, of whom 68 (49%; GA 26.9±1.5 weeks) succeeded on nCPAP with favourable outcome and 72 infants (51%; GA 26.3±1.4 weeks) failed nCPAP within 48 h at a median (IQR) age of 5.6 (3.3-19.3) h. History or initial blood gases were poor predictors of subsequent nCPAP failure. Intubation at fraction of inspired oxygen (FiO(2))≥0.35 versus 0.4 versus 0.45 instead of ≥0.6 would have resulted in unnecessary intubations of 16% versus 9% versus 6% of infants with nCPAP success but decreased the age at intubation of infants with nCPAP failure to 3.1 (2.2-5.2) versus 3.8 (2.5-8.7) versus 4.4 (2.7-10.9) h. CONCLUSIONS: Medical history or initial blood gas values are poor predictors of subsequent nCPAP failure. A threshold FiO(2) of ≥0.35-0.45 compared to ≥0.6 for intubation would shorten the time to surfactant delivery without a relevant increase in intubation rate. An individualised approach with a trial of early nCPAP and prompt intubation and surfactant treatment at low thresholds may be the best approach in very low birthweight infants.

[Data collection for quality assurance in neonatology: how do physicians compare to documentation specialists?]. / Datenerhebung für die Qualitätssicherung in der Neonatologie. Wer dokumentiert genauer: Arzte oder spezielle Dokumentationskräfte?

BACKGROUND: The quality of data collected for the German nationwide quality assurance program in neonatology is currently unknown. The aim of this study was to compare the quality of data collected by resident physicians with the quality of similar data collected by a dedicated research nurse. METHODS: Data for the German national quality assurance program in neonatology, derived from a cohort of 128 premature newborns with a birth weight <1500 g and/or a gestational age of <30 weeks born in the year 2003, were collected by residents taking care on these patients, and separately by a dedicated research nurse for the European Neonatal Network (EuroNeoNet). The data set collected for both networks included 44 common data items. The two data sets were compared, and any disagreement was double-checked using the chart of the baby to clarify which of the data entries was wrong. Furthermore, as data items are not equally important, a weighted analysis of all mistakes was performed. RESULTS: We found wrong data in 108/128 (84 %) of the data sets collected by the residents, and in 43/128 (34 %) of the data sets collected by the research nurse (p < 0.001). The weighted analysis revealed that residents made more mistakes in 30/44 of collected data items, whereas the research nurse did worse only in 1/44 data items. CONCLUSION: This study shows that the quality of data obtained by our resident physicians was worse than the quality of data obtained by our dedicated research nurse.

[Mortality and morbidity of very premature infants in Baden-Württemberg depending on hospital size. Is the current degree of regionalization adequate?]. / Mortalität und Morbidität sehr unreifer Frühgeborener in Baden-Württemberg in Abhängigkeit von der Klinikgrösse. Ist der derzeitige Grad der Regionalisierung ausreichend?

BACKGROUND: Regionalization of perinatal and neonatal care improves outcome. The aim of this study was to compare outcome in preterm infants with a gestational age (GA) < 32 weeks in relation to patient volume. METHODS: Outcome data from the state-wide neonatal quality assurance system from 2003 - 2004 from all infants treated in one of the five largest perinatal centers in Baden-Wuerttemberg were subtracted from the total dataset. Data derived from these five centers was compared with data from all other remaining NICU's in the state. RESULTS: Mortality was 33.3 % vs. 15.0 % (other NICU's vs. five perinatal centers; p < 0.001) for infants < 26 weeks GA, 11.4 % vs. 8.9 % (n. s.) for infants 26 - 27 weeks GA, and 2.5 % vs. 3.5 % (n. s.) for infants 28 - 31 weeks GA. When analyzed as one group of infants < 28 weeks GA, mortality was 20.1 vs. 12.1 % (p = 0.003). The rate of intraventricular hemorrhage degrees III-IV was 30.2 % vs. 18.6 % (p = 0.015) for infants < 26 weeks GA, 14.5 % vs. 10.2 % (n. s.) for infants 26 - 27 weeks GA, and 2.9 % vs. 2.5 % (n. s.) for infants 28 - 31 weeks GA. The rate of periventricular leukomalacia was 11.3 % vs. 6.7 % (p = 0.18) for infants < 26 weeks GA, 6.1 % vs. 2.8 % (n. s.) for infants 26 - 27 weeks GA, and 2.8 % vs. 2.3 %; (n. s.) for infants 28 - 31 weeks GA. CONCLUSION: This study supports the hypothesis, that regionalization of neonatal care for very immature infants to few perinatal centers with a large case load may improve survival of these infants, and may reduce morbidity, associated with long-term sequelae.

[Fulminant pneumococcal sepsis in a 13 months old child with congenital asplenia]. / Fulminante Pneumokokkensepsis bei einem 13 Monate alten Kleinkind mit angeborener familiärer Asplenie.

Asplenia may predispose to fulminant invasive infections caused by encapsulated bacteria. We observed a 13 months old child with (so far unknown) congenital familiar asplenia, who died from pneumococcal sepsis. General vaccination of all infants with pneumococcal conjugate vaccine may prevent this disease, which is associated with a high rate of mortality in infants with asplenia.

[Preserved spontaneous breathing during partial liquid ventilation. Results of experimental animal studies and their clinical implications]. / Erhaltene spontane Atemtätigkeit während partieller Flüssigkeitsbeatmung. Ergebnisse tierexperimenteller Studien und deren potentielle klinische Relevanz.

Controlled mechanical ventilation (CMV) may contribute to impaired hemodynamics in patients with respiratory failure. It is rational to assume that hybrid modalities of mechanical ventilation have fewer hemodynamic side-effects when spontaneous respiratory activity is allowed during the application of positive airway pressure. Partial liquid ventilation (PLV) has been shown to improve gas exchange in subjects with severe alveolar lung disease. We have shown that spontaneous respiratory efforts during proportional assist ventilation (PAV) is possible in experimental animals without lung disease whose lungs are partially filled with perfluorocarbons. In another series of experiments we demonstrated that PLV improves oxygenation and lung compliance in adult rabbits with severe surfactant deficiency, and in rabbits with meconium aspiration. In animals with meconium aspiration mortality, work of breathing and the degree of lung injury, as assessed by histological analysis, were reduced. In another two series of animals with and without surfactant deficiency spontaneous breathing supported by PAV was associated with increased cardiac output, stroke volume and oxygen transport, as compared to CMV after pharmacologically induced muscle paralysis. An increased arterial and venous pH in animals with surfactant deficiency during spontaneous breathing supported by PAV suggests improved tissue perfusion. Furthermore, gas exchange was improved during spontaneous breathing supported by PAV as compared to CMV and muscle paralysis.

Dynamics of breathing during partial liquid ventilation in spontaneously breathing rabbits supported by elastic and resistive unloading.

Partial liquid ventilation (PLV) has been shown to improve gas exchange in paralyzed animals and in humans with lung disease. This study tests the hypothesis that PLV combined with respiratory mechanical unloading results in stable ventilation and gas exchange in spontaneously breathing animals. Ten adult anesthetized, intubated, and spontaneously breathing rabbits received ventilatory support by respiratory mechanical unloading (Fi(O2) 1.0). Minute ventilation, respiratory rate, esophageal pressure, heart rate, and arterial blood pressure were recorded continuously during gas ventilation for 1 h. Next, 30 mL/kg of perfluorocarbon was instilled into the endotracheal tube. Thereafter, data were recorded again for 1 h (PLV). Arterial blood gases were obtained at the end of each period. Variability of recorded data was assessed by calculating coefficients of variation using data obtained each minute. Compared with gas ventilation, minute ventilation was larger during PLV (275 +/- 93 versus 368 +/- 89 mL/kg/min.; p < 0.01). This was because of a higher respiratory rate during PLV (58 +/- 23 versus 74 +/- 18 breaths/min; p < 0.05), while tidal volume was similar. Compared with gas ventilation, Pa(O2) was lower during PLV (61.31 +/- 5.32 versus 47.35 +/- 8.38 kPa; p < 0.05). Pa(CO2), peak esophageal pressure deflections, heart rate, mean arterial blood pressure, and coefficients of variation for minute ventilation, tidal volume, respiratory rate, and peak esophageal pressure were not significantly different between modes. Compliance was decreased and resistance and work of breathing were increased during PLV. We conclude that stable ventilation and gas exchange may be achieved during PLV combined with mechanical unloading in spontaneously breathing animals without lung disease.

Preserved spontaneous breathing improves cardiac output during partial liquid ventilation.

The aim of this study was to examine whether preserved spontaneous breathing (SB) supported by proportional-assist ventilation (PAV) would improve cardiac output (CO) during partial liquid ventilation (PLV) in rabbits with and without lung disease if compared with time-cycled, volume-controlled ventilation (CV) combined with muscle paralysis (MP). PLV was initiated in 17 healthy rabbits and 17 surfactant-depleted rabbits using 12 to 15 ml/kg of perfluorodecaline. Both ventilatory modes, SB+PAV and CV+MP, were applied in random sequence using a crossover design. CO was measured by thermodilution. CO was significantly higher during SB+PAV than during CV+MP: 136 +/- 21 ml/kg x min (mean +/- SD) versus 120 +/- 30 ml/kg x min (p = 0.004) in healthy rabbits, and 147 +/- 19 ml/kg x min versus 111 +/- 13 ml/kg x min (p < 0.0001) in surfactant-depleted rabbits, resulting in an improved oxygen delivery. This difference was mainly caused by a larger stroke volume during SB+PAV, whereas there was little change in heart rate. In surfactant-depleted rabbits, SB+PAV resulted in improved arterial blood pressure and arterial and mixed venous pH and in a higher PaO2 at the same level of PEEP and mean airway pressure. We conclude that during PLV, CO is higher during SB+PAV than during CV+MP, resulting in an improved oxygen delivery. In surfactant-depleted rabbits, improved CO, oxygen delivery, and arterial blood pressure resulted in higher pH, possibly reflecting improved tissue perfusion and oxygenation.

Patient-triggered ventilation in neonates: comparison of a flow-and an impedance-triggered system.

We conducted a study with the objective of comparing the performance of two different systems for patient-triggered ventilation in neonates (impedance versus flow/volume-triggered) by measuring response time, autotrigger and trigger failure rates, ventilation, and gas exchange. The two ventilator systems were applied in random order in 10 preterm neonates (median gestational age: 30.5 wk; range: 27 to 34 wk; body weight: 1,266 g; range: 840 to 2,240 g) using identical ventilator settings. The median (range) response time was 169 (98 to 305) ms for the impedance system and 115 (79 to 184) ms for the flow/volume system (p < 0.01). The longer and more variable response time of the impedance system was secondary to a phase lag of the impedance signal caused by chest wall distortion. Although 13.1 (0.2 to 29.4)% of mechanical breaths were autotriggered with the impedance system, there were no autotriggered breaths using the flow/volume system (p < 0.01). The rate of trigger failures was not significantly different with the two systems, at 1.2 (0 to 4.4)% (impedance) versus 3.1 (0 to 6.4)% (flow/volume). Minute ventilation was smaller with the impedance system (p < 0.001), because of the larger number of breaths triggered late in inspiration or during expiration. We conclude that the flow/volume-triggered system is less prone to autotriggering and has a shorter and more consistent response time than the impedance-triggered system. The impedance-triggered system is more susceptible to artifacts and chest wall distortion.

Spontaneous breathing during partial liquid ventilation in animals with meconium aspiration.

Partial liquid ventilation (PLV) has been shown to improve gas exchange in paralyzed animals and humans with lung disease. The present study tests the hypothesis that PLV improves gas exchange in spontaneously breathing animals with meconium aspiration supported by proportional assist ventilation. Twenty-five adult anesthetized intubated rabbits with experimental meconium aspiration were randomized to gas ventilation (GV) or PLV while being supported by proportional assist ventilation. Minute ventilation, tidal volume, respiratory rate, mean airway pressure, heart rate, and mean arterial and pulmonary arterial pressure were recorded continuously. Every 30 min, arterial blood gases were obtained, and lung compliance, airway resistance, work of breathing, and cardiac output were measured. Animals were sacrificed after 5 h to obtain lung histology. More PLV animals survived until the end of the study period. PaO(2) (14.5 +/- 4.5 versus 25.6 +/- 6.7 kPa; p < 0.01; GV versus PLV) and lung compliance (4.3 +/- 0.4 versus 6.1 +/- 1.2 mL.kPa(-1).kg(-1); p < 0.001) were improved during PLV, resulting in a lower work of breathing (5.3 +/- 2.8 versus 3.5 +/- 1.5 mL.kPa.kg(-1); p < 0.05) and less need for ventilatory support. Minute ventilation and respiratory rate were higher during GV versus PLV, resulting in a slightly lower PaCO(2) (3.9 +/- 0.5 versus 4.5 +/- 0.7 kPa; p < 0.05). Histologic evaluation showed more atelectasis, inflammatory changes, and hemorrhage in GV animals. Other parameters measured were similar. We conclude that PLV improves oxygenation, lung compliance, and survival and results in less lung injury in spontaneously breathing animals with meconium aspiration when supported by proportional assist ventilation.

Pulmonary administration of perfluorodecaline- gentamicin and perfluorodecaline- vancomycin emulsions.

The aim of this study was to examine pharmacokinetics and pulmonary antibiotic tissue concentrations (PATC) of gentamicin and vancomycin after intrapulmonary administration of a perfluorodecaline (PFD)-gentamicin and a PFD-vancomycin emulsion during partial liquid ventilation (PLV). PLV was initiated in 19 healthy rabbits and 18 surfactant-depleted rabbits. The animals were randomized to receive either 5 mg/kg gentamicin and 15 mg/kg vancomycin intravenously, or 5 mg/kg gentamicin intrapulmonary, or 15 mg/kg vancomycin intrapulmonary. Antibiotic plasma levels were measured after 15, 30, 45, and 60 min, and hourly thereafter. After 5 h animals were sacrificed and lungs were removed to evaluate PATC and histology. PATC were significantly higher after intrapulmonary administration of both gentamicin and vancomycin. In healthy rabbits, peak plasma concentrations were lower and 5 h plasma concentrations were higher after intrapulmonary administration, whereas plasma concentrations were not different in surfactant-depleted rabbits. There were no differences in lung histology, hemodynamics, lung mechanics, or gas exchange between the treatment groups. We conclude that during PLV, higher PATC can be achieved after intrapulmonary administration of PFD-antibiotic emulsions compared with intravenous administration of the same dose without apparent short-term adverse effects. We speculate that intrapulmonary antibiotic administration during PLV may be beneficial in treating severe pneumonia.

Partial liquid ventilation in severely surfactant-depleted, spontaneously breathing rabbits supported by proportional assist ventilation.

OBJECTIVE: We hypothesized that partial liquid ventilation (PLV) would improve oxygenation in nonparalyzed, surfactant-deficient rabbits breathing spontaneously while supported by proportional assist ventilation (PAV). This ventilation mode compensates for low pulmonary compliance and high resistance and thereby facilitates spontaneous breathing. DESIGN: Randomized trial. SETTING: University animal research facility. SUBJECTS: Twenty-six anesthetized New Zealand white rabbits weighing 2592 +/- 237g (mean +/- sd). INTERVENTIONS: After pulmonary lavage (target Pao2 <100 mm Hg on mechanical ventilation with 6 cm H2O of positive end-expiratory pressure [PEEP] and an Fio2 of 1.0), rabbits were randomized to PAV (PEEP of 8 cm H2O) with or without PLV. PLV rabbits received 25 mL/kg of perfluorocarbon by intratracheal infusion (1 mL/kg/min). Pao2, Paco2, tidal volume, respiratory rate, minute ventilation, mean airway pressure, arterial blood pressure, heart rate, pulmonary compliance, and airway resistance were measured. Evaporated perfluorocarbon was refilled every 30 mins in PLV animals. After 5 hrs, animals were killed and lungs were removed. Lung injury was evaluated using a histologic score. MAIN RESULTS: Pao2 and compliance were significantly higher in PLV rabbits compared with controls (p <.05, analysis of variance for repeated measures). All other parameters were similar in both groups. CONCLUSIONS: PLV improved oxygenation and pulmonary compliance in spontaneously breathing, severely surfactant-depleted rabbits supported by PAV. The severity of lung injury by histology was unaffected.