Achieving targeted pulse oximetry values in preterm infants in the delivery room.

OBJECTIVE: To determine whether resuscitation teams can better maintain newborn transitional oxygen saturation (SpO2) values within a prespecified target range using a graphical display of the targets and real-time SpO2 data compared with using only numerical oximeter values. STUDY DESIGN: Preterm neonates were enrolled in this prospective cohort evaluation of a change in practice. The Transitional Oxygen Targeting System (TOTS) plots real-time SpO2 values in relation to 10th and 50th percentile SpO2 curves, which provides a visual target. After introduction of the TOTS, the resuscitation team adjusted the fraction of inspired oxygen to maintain the SpO2 within the target range, and before its use neonates were resuscitated in attempt to target normal transitional SpO2 values without using the TOTS monitor. Duration of time within 10th-50th percentile values was compared between 2 cohorts, children evaluated with the TOTS and those not evaluated with the TOTS (controls). RESULTS: A total of 40 infants were enrolled, including 20 prospectively evaluated with the TOTS and 20 controls. Mean gestational age, birth weight, total resuscitation time, duration of supplemental oxygen administration, changes in oxygen concentration, and respiratory support provided were similar in the 2 groups. The TOTS cohort spent 52% of time within the target range; the control cohort, 37% (P = .03). CONCLUSION: SpO2 values were maintained within a specified target range for significantly longer in preterm neonates resuscitated using the TOTS display compared with those resuscitated without TOTS.

Bronchopulmonary dysplasia - associated pulmonary hypertension: An updated review.

Bronchopulmonary dysplasia (BPD) is the leading cause of chronic lung disease in infants and the commonest complication of prematurity. Advances in respiratory and overall neonatal care have increased the survival of extremely low gestational age newborns, leading to the continued high incidence of BPD. Pulmonary hypertension (PH) represents the severe form of the pulmonary vascular disease associated with BPD, and affects almost one-third of infants with moderate to severe BPD. PH responds suboptimally to pulmonary vasodilators and increases morbidity and mortality in BPD infants. An up-to-date knowledge of the pathogenesis, pathophysiology, diagnosis, treatment, and outcomes of BPD-PH can be helpful to develop meaningful and novel strategies to improve the outcomes of infants with this disorder. Therefore, our multidisciplinary team has attempted to thoroughly review and summarize the latest advances in BPD-PH in preventing and managing this morbid lung disorder of preterm infants.

RDS-NExT workshop: consensus statements for the use of surfactant in preterm neonates with RDS.

OBJECTIVE: To provide the best clinical practice guidance for surfactant use in preterm neonates with respiratory distress syndrome (RDS). The RDS-Neonatal Expert Taskforce (RDS-NExT) initiative was intended to add to existing evidence and clinical guidelines, where evidence is lacking, with input from an expert panel. STUDY DESIGN: An expert panel of healthcare providers specializing in neonatal intensive care was convened and administered a survey questionnaire, followed by 3 virtual workshops. A modified Delphi method was used to obtain consensus around topics in surfactant use in neonatal RDS. RESULT: Statements focused on establishing RDS diagnosis and indicators for surfactant administration, surfactant administration methods and techniques, and other considerations. After discussion and voting, consensus was achieved on 20 statements. CONCLUSION: These consensus statements provide practical guidance for surfactant administration in preterm neonates with RDS, with a goal to contribute to improving the care of neonates and providing a stimulus for further investigation to bridge existing knowledge gaps.

Mask versus Prongs for Nasal Continuous Positive Airway Pressure in Preterm Infants: A Systematic Review and Meta-Analysis.

Nasal continuous positive airway pressure (NCPAP) is an effective method of respiratory support for preterm infants. Nasal masks and binasal prongs are two interfaces available to deliver NCPAP, and it is unclear if one is superior to the other. We conducted a systematic review and meta-analysis, using the methodology recommended by the Cochrane Collaboration, to compare the efficacy and safety of nasal masks versus binasal prongs to deliver NCPAP in preterm infants <37 weeks of gestation. Ovid MEDLINE, Embase, Scopus, the Cochrane database, and PubMed were searched in February 2019. Seven trials met the inclusion criteria. Among preterm infants requiring NCPAP, the use of a nasal mask, compared to nasal prongs, decreased the rate of NCPAP failure within 72 h (RR 0.72, 95% CI 0.53-0.97; number needed to treat for an additional beneficial outcome [NNTB] 12.5, 95% CI 7.1-100; 5 trials, 576 participants; low-certainty evidence) and the incidence of nasal injury (RR 0.71, 95% CI 0.59-0.85; NNTB 8.3, 95% CI 5.6-16.7; 6 trials, 665 participants; low-certainty evidence). In a subgroup of preterm infants requiring NCPAP after resuscitation at birth, the use of a nasal mask decreased the incidence of moderate-to-severe bronchopulmonary dysplasia (RR 0.47, 95% CI 0.23-0.95; NNTB 16.7, 95% CI 9.1-100; 4 trials, 395 participants; very-low-certainty evidence) and the need for subsequent surfactant administration (RR 0.78, 95% CI 0.64-0.96; NNTB 8.33, 95% CI 4.54-33.33; 4 trials, 395 participants; low-certainty evidence). The use of nasal masks for preterm infants requiring NCPAP was associated with a reduction in NCPAP failure, need for surfactant administration, and moderate-to-severe bronchopulmonary dysplasia (low- to very-low-certainty evidence). Given the potential clinical benefit and minimal risk associated with a change in patient interface, nasal masks should be considered the preferred interface for NCPAP delivery in preterm infants.

Schedule-dependent synergy between the heat shock protein 90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin and doxorubicin restores apoptosis to p53-mutant lymphoma cell lines.

PURPOSE: Loss of p53 function impairs apoptosis induced by DNA-damaging agents used for cancer therapy. Here, we examined the effect of the heat shock protein 90 (HSP90) inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (DMAG) on doxorubicin-induced apoptosis in lymphoma. We aimed to establish the optimal schedule for administration of both drugs in combination and the molecular basis for their interaction. EXPERIMENTAL DESIGN: Isogenic lymphoblastoid and nonisogenic lymphoma cell lines differing in p53 status were exposed to each drug or combination. Drug effects were examined using Annexin V, active caspase-3, cell cycle, and cytotoxicity assays. Synergy was evaluated by median effect/combination index. Protein expression and kinase inhibition provided insight into the molecular mechanisms of drug interaction. RESULTS: Presence of mutant p53 conferred increased survival to single agents. Nevertheless, DMAG showed synergistic toxicity with doxorubicin independently of p53 status. Synergy required exposure to doxorubicin before DMAG. DMAG-mediated down-regulation of CHK1, a known HSP90 client, forced doxorubicin-treated cells into premature mitosis followed by apoptosis. A CHK1 inhibitor, SB-218078, reproduced the effect of DMAG. Administration of DMAG before doxorubicin resulted in G1-S arrest and protection from apoptosis, leading to additive or antagonistic interactions that were exacerbated by p53 mutation. CONCLUSIONS: Administration of DMAG to doxorubicin-primed cells induced premature mitosis and had a synergistic effect on apoptosis regardless of p53 status. These observations provide a rationale for prospective clinical trials and stress the need to consider schedule of exposure as a critical determinant of the overall response when DMAG is combined with chemotherapeutic agents for the treatment of patients with relapsed/refractory disease.

Time to achieve stable pulse oximetry values in VLBW infants in the delivery room.

OBJECTIVE: To study the time needed to obtain a reliable, functioning pulse oximeter signal during the resuscitation of very low birth weight (VLBW) infants. METHODS: This is a retrospective review of data from the resuscitation of preterm, VLBW infants at the University of California, San Diego Medical Center. Resuscitation teams consisted of a neonatal physician, a nurse, and respiratory therapist. Pulse oximetry was routinely used in all preterm deliveries. During resuscitation, the respiratory therapist attempted to place a pulse oximeter probe on the right hand or wrist immediately after birth. The BioPAC MP-150 Data Acquisition System was used to record analog data during the resuscitation, including the SpO2 value. From the analog tracing, the time at which a reliable pulse oximetry signal was obtained was determined. RESULTS: 50 VLBW (≤1500 g) preterm patients were studied. Mean gestational age was 27+4 weeks (range: 23-35 weeks). Mean birth weight was 920±287 g (range: 360-1445 g). Mean time to achieve functioning pulse oximetry was 79±42 s (range: 40-240 s). The median time was 67 s (interquartile range: 50-93 s). 86% of infants had a reliable SpO2 value obtained prior to 120 s of life. CONCLUSIONS: Our data show that an experienced respiratory therapist can apply a pulse oximeter and achieve reliable SpO2 values for the majority VLBW infants by 120 s of life as recommended by current NRP guidelines.