Early Cardiac and Cerebral Hemodynamics with Umbilical Cord Milking Compared with Delayed Cord Clamping in Infants Born Preterm.

OBJECTIVE: To evaluate changes in cerebral oxygenation, peripheral arterial oxygenation, respiratory status, and administered fraction of inspired oxygen during the first 10 minutes of life in premature infants receiving umbilical cord milking compared with delayed cord clamping (DCC). STUDY DESIGN: Premature infants born at 230/7 to 276/7 weeks of gestation were randomized to umbilical cord milking or DCC. A near infrared spectroscopy sensor, pulse oximeter, and electrocardiogram electrodes were placed. Pulse rate, cerebral tissue oxygenation, peripheral oxygen saturation, airway pressure, and fraction of inspired oxygen were collected for 10 minutes in the delivery room. Longitudinal models were used to compare effects of umbilical cord milking and DCC. RESULTS: Fifty-six infants had cerebral oximetry and advanced monitoring at birth. There was an increased incidence of severe intraventricular hemorrhage in infants who received umbilical cord milking compared with DCC (P = .0211). Longitudinal models suggested that peripheral oxygen saturation was higher in the umbilical cord milking group in the first 4 minutes (P = .0221) and that mean airway pressures were lower in the umbilical cord milking group after the first 7 minutes (P = .0072). No statistical differences were observed for fraction of inspired oxygen, cerebral tissue oxygenation, or heart rates. CONCLUSIONS: The data suggest that the rapid transfer of blood during umbilical cord milking may facilitate lung expansion with improved pulmonary blood flow, but may also increase cerebral blood flow, resulting in severe intraventricular hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03145142.

Success rate and duration of orotracheal intubation of premature infants by healthcare providers with different levels of experience using a video laryngoscope as compared to direct laryngoscopy in a simulation-based setting.

Background: Endotracheal intubation of very low birth weight infants (VLBWI) is an essential procedure in NICUs, but intubation experience is often limited. Video laryngoscopy (VL) has been described as a tool to improve intubation skills, but studies in high-risk neonatal populations are limited. Objective: The aim of this study was to investigate whether VL is a useful tool to support airway management in high-risk premature infants with inexperienced operators. Methods: In this crossover study predominantly inexperienced participants were exposed in random sequence to VL and conventional direct laryngoscopy (DL) for endotracheal intubation of a VLBWI simulation manikin to measure total time, number of attempts, success rate on first attempt, view of the vocal cords and perceived subjective safety until successful intubation. Results: In our study group of 94 participants there was no significant difference in the total time (mean VL: 34 s (±24 s); DL: 37 s (±28 s), p = 0.246), while the number of intubation attempts using VL was significantly lower (mean VL: 1.22 (±0.53); DL: 1.37 (±0.60), p = 0.023). Success rate of VL during the first attempt was significantly higher (VL: 84%; DL 69%, p = 0.016), view of the vocal cords was significantly better and perceived subjective safety was increased using VL. Conclusions: Our study results suggest that with rather inexperienced operators, VL can be a useful tool to increase rate of successful endotracheal intubation of VLBWI and to improve their perceived safety during the procedure, which may have an impact on mortality and/or morbidity.

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.

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.

Effect of Different Respiratory Modes on Return of Spontaneous Circulation in a Newborn Piglet Model of Hypoxic Cardiac Arrest.

BACKGROUND: There are no clear evidence-based recommendations on the use of different techniques of respiratory support and chest compressions (CC) during neonatal cardiopulmonary resuscitation (CPR). OBJECTIVES: To determine the effects of different respiratory support strategies along with CC representing clinical practice on the return of spontaneous circulation (ROSC) in hypoxic newborn piglets with cardiac arrest. We hypothesized that use of a T-piece resuscitator (TPR) providing positive end-expiratory pressure (PEEP) reduces time to ROSC as compared to a self-inflating bag (SIB) without PEEP. Furthermore, we explored the effects of a ventilator providing inflations without synchrony to CC. METHODS: Thirty-three newborn piglets were exposed to hypoxia until asystole occurred and randomized into three groups and resuscitated according to ILCOR guidelines: group 1 = TPR [peak inspiratory pressure (PIP)/PEEP of 25/5 cm H2O, rate 30/min], inflations interposed between CC (3:1 ratio); group 2 = SIB (PIP of 25 cm H2O without PEEP, rate 30/min), inflations interposed between CC (3:1 ratio), and group 3 = ventilator (PIP/PEEP of 25/5 cm H2O, rate 30/min), CC were applied with a rate of 120/min without synchrony to inflations. Animals were supported for 120 min after ROSC. Primary outcome was time to ROSC. RESULTS: All animals achieved ROSC. We found no significant difference in time to ROSC between groups [median (IQR); TPR: 150 s (150-210); SIB: 150 s (120-180); ventilator: 180 s (150-345)]. There was no difference in use of epinephrine, in blood gases or hemodynamic parameters during the 120-min observation time after ROSC. CONCLUSIONS: We found no significant effect of different respiratory support strategies during CPR on ROSC.

Different Techniques of Respiratory Support Do Not Significantly Affect Gas Exchange during Cardiopulmonary Resuscitation in a Newborn Piglet Model.

BACKGROUND: There are no evidence-based recommendations on the use of different techniques of respiratory support and chest compressions (CC) during neonatal cardiopulmonary resuscitation (CPR). OBJECTIVES: We studied the short-term effects of different ventilatory support strategies along with CC representing clinical practice on gas exchange [arterial oxygen saturation (SaO2), arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2)], hemodynamics and cerebral oxygenation. We hypothesized that in newborn piglets with cardiac arrest, use of a T-piece resuscitator (TPR) providing positive end-expiratory pressure (PEEP) improves gas exchange as measured by SaO2 during CPR as compared to using a self-inflating bag (SIB) without PEEP. Furthermore, we explored the effects of a mechanical ventilator without synchrony to CC. METHODS: Thirty newborn piglets with asystole were randomized into three groups and resuscitated for 20 min [fraction of inspired oxygen (FiO2) = 0.21 for 10 min and 1.0 thereafter]. Group 1 received ventilation using a TPR [peak inspiratory pressure (PIP)/PEEP of 20/5 cm H2O, rate 30/min] with inflations interposed between CC (3:1 ratio). Group 2 received ventilation using a SIB (PIP of 20 cm H2O without PEEP, rate 30/min) with inflations interposed between CC (3:1 ratio). Group 3 received ventilation using a mechanical ventilator (PIP/PEEP of 20/5 cm H2O, rate 30/min). CC were applied with a rate of 120/min without synchrony to inflations. RESULTS: We found no significant differences in SaO2 between the three groups. However, there was a trend toward a higher SaO2 [TPR: 28.0% (22.3-40.0); SIB: 23.7% (13.4-52.3); ventilator: 44.1% (39.2-54.3); median (interquartile range)] and a lower PaCO2 [TPR: 95.6 mm Hg (82.1-113.6); SIB: 100.8 mm Hg (83.0-108.0); ventilator: 74.1 mm Hg (68.5-83.1); median (interquartile range)] in the mechanical ventilator group. CONCLUSIONS: We found no significant effect on gas exchange using different respiratory support strategies during CPR.

Very low tidal volume ventilation with associated hypercapnia--effects on lung injury in a model for acute respiratory distress syndrome.

BACKGROUND: Ventilation using low tidal volumes with permission of hypercapnia is recommended to protect the lung in acute respiratory distress syndrome. However, the most lung protective tidal volume in association with hypercapnia is unknown. The aim of this study was to assess the effects of different tidal volumes with associated hypercapnia on lung injury and gas exchange in a model for acute respiratory distress syndrome. METHODOLOGY/PRINCIPAL FINDINGS: In this randomized controlled experiment sixty-four surfactant-depleted rabbits were exposed to 6 hours of mechanical ventilation with the following targets: Group 1: tidal volume = 8-10 ml/kg/PaCO(2) = 40 mm Hg; Group 2: tidal volume = 4-5 ml/kg/PaCO(2) = 80 mm Hg; Group 3: tidal volume = 3-4 ml/kg/PaCO(2) = 120 mm Hg; Group 4: tidal volume = 2-3 ml/kg/PaCO(2) = 160 mm Hg. Decreased wet-dry weight ratios of the lungs, lower histological lung injury scores and higher PaO(2) were found in all low tidal volume/hypercapnia groups (group 2, 3, 4) as compared to the group with conventional tidal volume/normocapnia (group 1). The reduction of the tidal volume below 4-5 ml/kg did not enhance lung protection. However, oxygenation and lung protection were maintained at extremely low tidal volumes in association with very severe hypercapnia and no adverse hemodynamic effects were observed with this strategy. CONCLUSION: Ventilation with low tidal volumes and associated hypercapnia was lung protective. A tidal volume below 4-5 ml/kg/PaCO(2) 80 mm Hg with concomitant more severe hypercapnic acidosis did not increase lung protection in this surfactant deficiency model. However, even at extremely low tidal volumes in association with severe hypercapnia lung protection and oxygenation were maintained.