Chest compressions in newborn infants: a scoping review.

AIM: The International Liaison Committee on Resuscitation Neonatal Life Support Task Force undertook a scoping review of the literature to identify evidence relating to neonatal cardiopulmonary resuscitation. METHODS: MEDLINE complete, EMBASE and Cochrane database of Systematic reviews were searched from inception to November 2021. Two authors screened titles and abstracts and full text reviewed. Studies were eligible for inclusion if they were peer-reviewed and assessed one of five aspects of chest compression in the newborn infant including: (1) heart rate thresholds to start chest compressions (CC), (2) compression to ventilation ratio (C:V ratio), (3) CC technique, (4) oxygen use during CC and 5) feedback devices to optimise CC. RESULTS: Seventy-four studies were included (n=46 simulation, n=24 animal and n=4 clinical studies); 22/74 were related to compression to ventilation ratios, 29/74 examined optimal technique to perform CC, 7/74 examined oxygen delivery and 15/74 described feedback devices during neonatal CC. CONCLUSION: There were very few clinical studies and mostly manikin and animal studies. The findings either reinforced or were insufficient to change previous recommendations which included to start CC if heart rate remains <60/min despite adequate ventilation, using a 3:1 C:V ratio, the two-thumb encircling technique and 100% oxygen during CC.

Perinatal management: Lessons learned from the neonatal research network.

Recent contributions of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) regarding obstetrical perinatal interventions and neonatal delivery room practices include the following: the impact of multiple antepartum factors including maternal diabetes, hypertension, obesity and mode of delivery on outcomes of extremely preterm newborns, effects of delayed delivery interval for extremely preterm multiples, effects of antenatal steroids on preterm newborn outcomes and the impact of antenatal magnesium sulfate therapy on neurodevelopmental outcomes for extremely preterm infants. NRN studies also contribute important evidence for neonatal delivery room resuscitation guidelines including umbilical cord management and maintenance of euthermia immediately after birth. The updated NRN outcome calculator helps better counsel families regarding possible outcomes for the most immature newborns if resuscitation is attempted at birth. Thus, the NRN provides substantial information regarding effects of perinatal management on newborn infants.

Chest compressions and medications during neonatal resuscitation.

Prolonged resuscitation in neonates, although quite rare, may occur in response to profound intractable bradycardia as a result of asphyxia. In these instances, chest compressions and medications may be necessary to facilitate return of spontaneous circulation. While performing chest compressions, the two thumb method is preferred over the two finger technique, although several newer approaches are under investigation. While the ideal compression to ventilation ratio is still uncertain, a 3:1 ratio remains the recommendation by the Neonatal Resuscitation Program. Use of feedback mechanisms to optimize neonatal cardiopulmonary resuscitation (CPR) show promise and are currently under investigation. While performing optimal cardiac compressions to pump blood, use of medications to restore spontaneous circulation will likely be necessary. Current recommendations are that epinephrine, an endogenous catecholamine be used preferably intravenously or by intraosseous route, with the dose repeated every 3-5 minutes until return of spontaneous circulation. Finally, while the need for volume replacement is rare, it may be considered in instances of acute blood loss or poor response to resuscitation.

Drugs in the delivery room.

The need for cardiopulmonary resuscitation in newborns is quite rare, as most non-vigorous infants respond well to effective ventilation. For the minority of babies who do not respond to adequate ventilation, chest compressions are necessary using the preferred two thumb technique. Since effective ventilation remains a key component to successful resuscitation, chest compressions are coordinated with ventilations in a 3:1 ratio. If despite adequate ventilation and compressions, the heart rate remains below 60 beats per minute, epinephrine is indicated. The intravenous route is preferred over the endotracheal route and the recommended dose of epinephrine is 0.01-0.03 mg/kg. This can be repeated every 3-5 min until return of spontaneous circulation is achieved. In rare instances, when there is no response to these above measures and in infants who show evidence of significant hypovolemia, volume replacement should be considered.

CXCR4 blockade attenuates hyperoxia-induced lung injury in neonatal rats.

BACKGROUND: Lung inflammation is a key factor in the pathogenesis of bronchopulmonary dysplasia (BPD). Stromal-derived factor-1 (SDF-1) and its receptor chemokine receptor 4 (CXCR4) modulate the inflammatory response. It is not known if antagonism of CXCR4 alleviates lung inflammation in neonatal hyperoxia-induced lung injury. OBJECTIVE: We aimed to determine whether CXCR4 antagonism would attenuate lung injury in rodents with experimental BPD by decreasing pulmonary inflammation. METHODS: Newborn rats exposed to normoxia (room air, RA) or hyperoxia (FiO2 = 0.9) from postnatal day 2 (P2) to P16 were randomized to receive the CXCR4 antagonist, AMD3100 or placebo (PL) from P5 to P15. Lung alveolarization, angiogenesis and inflammation were evaluated at P16. RESULTS: Compared to the RA pups, hyperoxic PL pups had a decrease in alveolarization, reduced lung vascular density and increased lung inflammation. In contrast, AMD3100-treated hyperoxic pups had improved alveolarization and increased angiogenesis. This improvement in lung structure was accompanied by a decrease in the macrophage and neutrophil counts in the bronchoalveolar lavage fluid and reduced lung myeloperoxidase activity. CONCLUSION: CXCR4 antagonism decreases lung inflammation and improves alveolar and vascular structure in neonatal rats with experimental BPD. These findings suggest a novel therapeutic strategy to alleviate lung injury in preterm infants with BPD.

Bone marrow-derived c-kit+ cells attenuate neonatal hyperoxia-induced lung injury.

Recent studies suggest that bone marrow (BM)-derived stem cells have therapeutic efficacy in neonatal hyperoxia-induced lung injury (HILI). c-kit, a tyrosine kinase receptor that regulates angiogenesis, is expressed on several populations of BM-derived cells. Preterm infants exposed to hyperoxia have decreased lung angiogenesis. Here we tested the hypothesis that administration of BM-derived c-kit(+) cells would improve angiogenesis in neonatal rats with HILI. To determine whether intratracheal (IT) administration of BM-derived c-kit(+) cells attenuates neonatal HILI, rat pups exposed to either normobaric normoxia (21% O2) or hyperoxia (90% O2) from postnatal day (P) 2 to P15 were randomly assigned to receive either IT BM-derived green fluorescent protein (GFP)(+) c-kit(-) cells (PL) or BM-derived GFP(+) c-kit(+) cells on P8. The effect of cell therapy on lung angiogenesis, alveolarization, pulmonary hypertension, vascular remodeling, cell proliferation, and apoptosis was determined at P15. Cell engraftment was determined by GFP immunostaining. Compared to PL, the IT administration of BM-derived c-kit(+) cells to neonatal rodents with HILI improved alveolarization as evidenced by increased lung septation and decreased mean linear intercept. This was accompanied by an increase in lung vascular density, a decrease in lung apoptosis, and an increase in the secretion of proangiogenic factors. There was no difference in pulmonary vascular remodeling or the degree of pulmonary hypertension. Confocal microscopy demonstrated that 1% of total lung cells were GFP(+) cells. IT administration of BM-derived c-kit(+) cells improves lung alveolarization and angiogenesis in neonatal HILI, and this may be secondary to an improvement in the lung angiogenic milieu.

Stem cell factor improves lung recovery in rats following neonatal hyperoxia-induced lung injury.

BACKGROUND: Stem cell factor (SCF) and its receptor, c-kit, are modulators of angiogenesis. Neonatal hyperoxia-induced lung injury (HILI) is characterized by disordered angiogenesis. The objective of this study was to determine whether exogenous SCF improves recovery from neonatal HILI by improving angiogenesis. METHODS: Newborn rats assigned to normoxia (RA: 20.9% O2) or hyperoxia (90% O2) from postnatal day (P) 2 to 15, received daily injections of SCF 100 µg/kg or placebo (PL) from P15 to P21. Lung morphometry was performed at P28. Capillary tube formation in SCF-treated hyperoxia-exposed pulmonary microvascular endothelial cells (HPMECs) was determined by Matrigel assay. RESULTS: As compared with RA, hyperoxic-PL pups had decrease in alveolarization and in lung vascular density, and this was associated with increased right ventricular systolic pressure (RVSP), right ventricular hypertrophy, and vascular remodeling. In contrast, SCF-treated hyperoxic pups had increased angiogenesis, improved alveolarization, and attenuation of pulmonary hypertension as evidenced by decreased RVSP, right ventricular hypertrophy, and vascular remodeling. Moreover, in an in vitro model, SCF increased capillary tube formation in hyperoxia-exposed HPMECs. CONCLUSION: Exogenous SCF restores alveolar and vascular structure in neonatal rats with HILI by promoting neoangiogenesis. These findings suggest a new strategy to treat lung diseases characterized by dysangiogenesis.