Lung injury after asphyxia and hemorrhagic shock in newborn piglets: Analysis of structural and inflammatory changes.

OBJECTIVE: Asphyxia of newborns is a severe and frequent challenge of the peri- and postnatal period. The purpose of this study was to study early morphological, immunological and structural alterations in lung tissue after asphyxia and hemorrhage (AH). METHODS: 44 neonatal piglets (age 32 hrs) underwent asphyxia and hemorrhage (AH) and were treated according to the international liaison committee of resuscitation (ILCOR) guidelines. For this study, 15 piglets (blood transfusion (RBC) n = 9; NaCl n = 6, mean age 31 hrs) were randomly picked. 4 hours after ROSC (return of spontaneous circulation), lung tissue and blood samples were collected. RESULTS: An elevation of myeloperoxidase (MPO) activity was observed 4 hrs after AH accompanied by an increase of surfactant D after RBC treatment. After AH tight junction proteins Claudin 18 and junctional adhesion molecule 1 (JAM1) were down-regulated, whereas Occludin was increased. Furthermore, after AH and RBC treatment dephosphorylated active form of Connexin 43 was increased. CONCLUSIONS: AH in neonatal pigs is associated with early lung injury, inflammation and alterations of tight junctions (Claudin, Occludin, JAM-1) and gap junctions (Connexin 43) in lung tissue, which contributes to the development of lung edema and impaired function.

Tissue damage in the heart after cardiac arrest induced by asphyxia and hemorrhage in newborn pigs.

BACKGROUND: Asphyxia of newborns is a severe and frequent challenge of the peri- and postnatal period. METHODS: Forty-four neonatal piglets underwent asphyxia and hemorrhage (AH), followed by resuscitation with blood or crystalloid transfusion. In this study, 15 piglets (blood n = 9, NaCl n = 6, mean age 31 h) were randomly chosen. Four hours after return of spontaneous circulation, heart tissue and blood were collected. Analyses of heart fatty acid binding protein (HFABP), cardiac troponin I (TnI) levels, and activation of the complement system were performed. Histological staining for connexin 43 (Cx43) and complement C5a receptor 1 (C5aR1) was performed. RESULTS: Following AH, systemic elevation of cardiac TnI and HFABP revealed cardiac damage in both groups. Systemic activation of the complement system and the appearance of extracellular histones in plasma of the blood transfusion group were observed. The Cx43 was translocated from the intercalated discs to the cytosol after AH. Cardiac glycogen concentration was reduced in both groups. A significant reduction of C5aR1 in the left ventricle and a significant elevation of the heart injury score were investigated after blood transfusion. CONCLUSION: AH leads to alteration of the heart, particularly in Cx43 and glycogen reserves, as well as local inflammation.

Effects of a new device for automated closed loop control of inspired oxygen concentration on fluctuations of arterial and different regional organ tissue oxygen saturations in preterm infants.

OBJECTIVE: To assess the efficacy of a newly developed system for closed loop control of the fraction of inspired oxygen (FiO2) on variation of arterial (SpO2) and on regional tissue oxygen saturation (StO2) in preterm infants with fluctuations in SpO2. DESIGN: Randomised crossover trial comparing automated (auto) to manual FiO2 adjustment (manual) during two consecutive 24 hours periods using a Sophie infant ventilator (SPO2C). SETTING: Tertiary university medical centre. PATIENTS: Twelve very low birthweight infant (VLBWI) (gestational age (median; IQR): (25; 23-26 weeks); birth weight (mean±SD): (667±134 g); postnatal age (mean±SD): (31.5±14 days)). MAIN OUTCOME MEASURE: Time within SpO2 target range. RESULTS: There was an increase in time within the intended SpO2 target range (88%-96%) during auto as compared with manual mode (77.8%±7.1% vs 68.5%±7.7% (mean±SD), p<0.001) and a decrease in time below the SpO2 target during the auto period (18.1%±6.4% vs 25.6%±7.6%; p<0.01). There was a dramatic reduction in events with an SpO2 <88% with >180 s duration: (2 (0-10) vs 10 (0-37) events, p<0.001) and the need for manual adjustments. The time the infants spent above the intended arterial oxygen range (4.1%±3.8% vs 5.9%±3.6%), median FiO2, mean SpO2 over time and StO2 in the brain, liver and kidney did not differ significantly between the two periods. CONCLUSIONS: Closed-loop FiO2 using SPO2C significantly increased time of arterial SpO2 within the intended range in VLBWI and decreased the need for manual adjustments when compared with the routine adjustment by staff members. StO2 was not significantly affected by the mode of oxygen control.

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.

Effects of Synchronization during Noninvasive Intermittent Mandatory Ventilation in Preterm Infants with Respiratory Distress Syndrome Immediately after Extubation.

BACKGROUND: Noninvasive ventilation is increasingly used in very-low-birth-weight infants (VLBWI) to reduce complications that occur with invasive ventilation. However, the physiological effects of synchronization during noninvasive nasal intermittent mandatory ventilation (IMV) have not been tested in VLBWI immediately after extubation. OBJECTIVE: We aimed to study the short-term effects of synchronized nasal IMV (S-NIMV) compared to nonsynchronized nasal IMV (NIMV) on breathing effort as measured by phasic esophageal pressure (Pe) deflection, spontaneous respiratory rate (RR), gas exchange, cerebral tissue oxygen saturation (StO2) and intermittent episodes of bradycardia or hypoxemia in VLBWI recovering from respiratory distress syndrome (RDS). METHODS: Fourteen VLBWI recovering from RDS were studied using a randomized cross-over design during both S-NIMV and NIMV (of 2 h each) immediately after extubation. RESULTS: Phasic Pe deflection, spontaneous RR and transcutaneous PCO2 decreased significantly while transcutaneous PO2 and synchrony rate (defined as peak ventilator pressure delivered within the first half of spontaneous inspiration) increased significantly during S-NIMV compared to during NIMV. There was no difference in blood pressure, average arterial oxygen saturation (SpO2), cerebral StO2, fractional tissue oxygen extraction of the brain and severe bradycardia (defined as time with a heart rate <100 beats/min lasting ≥10 s) and in hypoxemic episodes (SpO2 <80%) between the two modes. CONCLUSION: Synchronization during nasal ventilation immediately after extubation in VLBWI recovering from RDS improved gas exchange and decreased the respiratory effort, and it could therefore be considered to provide a more efficient respiratory support and synchrony.

Effects of automated adjustment of the inspired oxygen on fluctuations of arterial and regional cerebral tissue oxygenation in preterm infants with frequent desaturations.

OBJECTIVE: To assess the effect of automated adjustment of the inspired oxygen fraction (FiO2) on arterial oxygen saturation (SpO2) and cerebral tissue oxygen saturation (SctO2) in very low birth weight infants with frequent fluctuations in oxygenation. STUDY DESIGN: Fifteen infants (median gestational age, 25 weeks [range, 23-28 weeks]; median age, 34 days [range, 19-74 days]) were assigned in random sequence to 24 hours of automated adjustment of FiO2 or manual adjustment of FiO2. Primary outcome measurements were time within the SpO2 target range and the area under the curve above and below a defined SctO2 range. RESULTS: Percentage of time within the SpO2 target range increased during automated FiO2 control (76.3% ± 9.2% vs 69.1% ± 8.2% for manual; P < .01). Prolonged episodes with SpO2 <88% of >60 seconds duration (median, 115 episodes [range, 67-240] vs 54 episodes [range, 7-184]; P < .01) and of >180 seconds duration (median, 13 episodes [range, 6-39] vs 2 episodes [range, 0-5]; P < .01) decreased significantly during the automated period. Percentage of time with SpO2 >96% decreased during automated control (6.6% ± 4.4% vs 10.4% ± 3.3%; P < .02). There was no significant difference in FiO2 exposure. The area (deviation × time) below and above the defined SctO2 threshold did not differ between the 2 periods (median, 59.7%*seconds [range, 17.2%-208.3%] for manual vs 49.0%*seconds [range, 4.3%-193.7%] for automated; P = .36). CONCLUSION: Automated FiO2 control in preterm infants with frequent SpO2 fluctuations significantly increased the time within the SpO2 target range and reduced the incidence of prolonged hypoxemic events compared with manual FiO2 adjustment, but did not significantly affect cerebral tissue oxygenation.