Peter G Davis

Part 11: Neonatal Resuscitation 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations

2010;126;e1319-e1344; originally published online Oct 18, 2010; Pediatrics COLLABORATORS CHAPTER Sithembiso Velaphi and on behalf of the NEONATAL RESUSCITATION Sam Richmond, Wendy M. Simon, Nalini Singhal, Edgardo Szyld, Masanori Tamura, Chameides, Jay P. Goldsmith, Ruth Guinsburg, Mary Fran Hazinski, Colin Morley, Jeffrey M. Perlman, Jonathan Wyllie, John Kattwinkel, Dianne L. Atkins, Leon Recommendations Resuscitation and Emergency Cardiovascular Care Science With Treatment Neonatal Resuscitation: 2010 International Consensus on Cardiopulmonary http://www.pediatrics.org/cgi/content/full/126/5/e1319 located on the World Wide Web at: The online version of this article, along with updated information and services, is rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275. Grove Village, Illinois, 60007. Copyright

Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants.

BACKGROUND The prophylactic administration of indomethacin reduces the frequency of patent ductus arteriosus and severe intraventricular hemorrhage in very-low-birth-weight infants (those with birth weights below 1500 g). Whether prophylaxis with indomethacin confers any long-term benefits that outweigh the risks of drug-induced reductions in renal, intestinal, and cerebral blood flow is not known. METHODS Soon after they were born, we randomly assigned 1202 infants with birth weights of 500 to 999 g (extremely low birth weight) to receive either indomethacin (0.1 mg per kilogram of body weight) or placebo intravenously once daily for three days. The primary outcome was a composite of death, cerebral palsy, cognitive delay, deafness, and blindness at a corrected age of 18 months. Secondary long-term outcomes were hydrocephalus necessitating the placement of a shunt, seizure disorder, and microcephaly within the same time frame. Secondary short-term outcomes were patent ductus arteriosus, pulmonary hemorrhage, chronic lung disease, ultrasonographic evidence of intracranial abnormalities, necrotizing enterocolitis, and retinopathy. RESULTS Of the 574 infants with data on the primary outcome who were assigned to prophylaxis with indomethacin, 271 (47 percent) died or survived with impairments, as compared with 261 of the 569 infants (46 percent) assigned to placebo (odds ratio, 1.1; 95 percent confidence interval, 0.8 to 1.4; P=0.61). Indomethacin reduced the incidence of patent ductus arteriosus (24 percent vs. 50 percent in the placebo group; odds ratio, 0.3; P<0.001) and of severe periventricular and intraventricular hemorrhage (9 percent vs. 13 percent in the placebo group; odds ratio, 0.6; P=0.02). No other outcomes were altered by the prophylactic administration of indomethacin. CONCLUSIONS In extremely-low-birth-weight infants, prophylaxis with indomethacin does not improve the rate of survival without neurosensory impairment at 18 months, despite the fact that it reduces the frequency of patent ductus arteriosus and severe periventricular and intraventricular hemorrhage.

Resuscitation of newborn infants with 100% oxygen or air: a systematic review and meta-analysis

BACKGROUND International consensus statements for resuscitation of newborn infants recommend provision of 100% oxygen with positive pressure if assisted ventilation is required. However, 100% oxygen exacerbates reperfusion injury in animals and reduces cerebral perfusion in newborn babies. We aimed to establish whether resuscitation with air decreased mortality or neurological disability in newborn infants compared with 100% oxygen. METHODS We did a systematic review and meta-analysis of trials that compared resuscitation with air versus 100% oxygen, using the methods of the Cochrane Collaboration. We combined data for similar outcomes in the analysis where appropriate, using a fixed-effects model. FINDINGS Five trials (two masked and three unmasked), consisting of 1302 newborn infants, fulfilled the inclusion criteria. Most babies were born at or near term in developing countries. In the three unmasked studies, infants resuscitated with room air who remained cyanotic and bradycardic were switched to 100% oxygen at 90 s. The masked studies allowed crossover to the other gas during the first minutes of life. Although no individual trial showed a difference in mortality, the pooled analysis showed a significant benefit for infants resuscitated with air (relative risk 0.71 [95% CI 0.54 to 0.94], risk difference -0.05 [-0.08 to -0.01]). The effect on long-term development could not be reliably determined because of methodological limitations in the one study that followed up infants beyond 12 months of age. INTERPRETATION For term and near-term infants, we can reasonably conclude that air should be used initially, with oxygen as backup if initial resuscitation fails. The effect of intermediate concentrations of oxygen at resuscitation needs to be investigated. Future trials should include and stratify for premature infants.

Defining the reference range for oxygen saturation for infants after birth.

OBJECTIVE: The goal was to define reference ranges for pulse oxygen saturation (Spo2) values in the first 10 minutes after birth for infants who received no medical intervention in the delivery room. METHODS: Infants were eligible if a member of the research team was available to record Spo2 immediately after birth. Infants were excluded if they received supplemental oxygen or any type of assisted ventilation. Spo2 was measured with a sensor applied to the right hand or wrist as soon as possible after birth; data were collected every 2 seconds. RESULTS: We studied 468 infants and recorded 61650 Spo2 data points. The infants had a mean ± SD gestational age of 38 ± 4 weeks and birth weight of 2970 ± 918 g. For all 468 infants, the 3rd, 10th, 50th, 90th, and 97th percentile values at 1 minute were 29%, 39%, 66%, 87%, and 92%, respectively, those at 2 minutes were 34%, 46%, 73%, 91%, and 95%, and those at 5 minutes were 59%, 73%, 89%, 97%, and 98%. It took a median of 7.9 minutes (interquartile range: 5.0–10 minutes) to reach a Spo2 value of >90%. Spo2 values for preterm infants increased more slowly than those for term infants. We present percentile charts for all infants, term infants of ≥37 weeks, preterm infants of 32 to 36 weeks, and extremely preterm infants of <32 weeks. CONCLUSION: These data represent reference ranges for Spo2 in the first 10 minutes after birth for preterm and term infants.

Survival Without Disability to Age 5 Years After Neonatal Caffeine Therapy for Apnea of Prematurity

CONTEXT Very preterm infants are prone to apnea and have an increased risk of death or disability. Caffeine therapy for apnea of prematurity reduces the rates of cerebral palsy and cognitive delay at 18 months of age. OBJECTIVE To determine whether neonatal caffeine therapy has lasting benefits or newly apparent risks at early school age. DESIGN, SETTING, AND PARTICIPANTS Five-year follow-up from 2005 to 2011 in 31 of 35 academic hospitals in Canada, Australia, Europe, and Israel, where 1932 of 2006 participants (96.3%) had been enrolled in the randomized, placebo-controlled Caffeine for Apnea of Prematurity trial between 1999 and 2004. A total of 1640 children (84.9%) with birth weights of 500 to 1250 g had adequate data for the main outcome at 5 years. MAIN OUTCOME MEASURES Combined outcome of death or survival to 5 years with 1 or more of motor impairment (defined as a Gross Motor Function Classification System level of 3 to 5), cognitive impairment (defined as a Full Scale IQ<70), behavior problems, poor general health, deafness, and blindness. RESULTS The combined outcome of death or disability was not significantly different for the 833 children assigned to caffeine from that for the 807 children assigned to placebo (21.1% vs 24.8%; odds ratio adjusted for center, 0.82; 95% CI, 0.65-1.03; P = .09). The rates of death, motor impairment, behavior problems, poor general health, deafness, and blindness did not differ significantly between the 2 groups. The incidence of cognitive impairment was lower at 5 years than at 18 months and similar in the 2 groups (4.9% vs 5.1%; odds ratio adjusted for center, 0.97; 95% CI, 0.61-1.55; P = .89). CONCLUSION Neonatal caffeine therapy was no longer associated with a significantly improved rate of survival without disability in children with very low birth weights who were assessed at 5 years.

Impact of Postnatal Systemic Corticosteroids on Mortality and Cerebral Palsy in Preterm Infants: Effect Modification by Risk for Chronic Lung Disease

Objective. In preterm infants, chronic lung disease (CLD) is associated with an increased risk for cerebral palsy (CP). However, systemic postnatal corticosteroid therapy to prevent or treat CLD, although effective in improving lung function, may cause CP. The objective of this study was to determine the effect of systemic postnatal corticosteroid treatment on death and CP and to assess any modification of effect arising from risk for CLD. Methods. Randomized, controlled trials of postnatal corticosteroid therapy for prevention or treatment of CLD in preterm infants that reported rates of both mortality and CP were reviewed and their data were synthesized. Twenty studies with data on 1721 randomized infants met eligibility criteria. The relationship between the corticosteroid effect on the combined outcome, death or CP, and the risk for CLD in control groups was analyzed by weighted meta-regression. Results. Among all infants who were randomized, a significantly higher rate of CP after corticosteroid treatment (typical risk difference [RD]: 0.05; 95% confidence interval [CI]: 0.02, 0.08) was partly offset by a nonsignificant reduction in mortality (typical RD: −0.02; 95% CI: −0.06 to 0.02). Consequently, there was no significant effect of corticosteroid treatment on the combined rate of mortality or CP (typical RD: 0.03; 95% CI: −0.01 to 0.08). However, on meta-regression, there was a significant negative relationship between the treatment effect on death or CP and the risk for CLD in control groups. With risks for CLD below 35%, corticosteroid treatment significantly increased the chance of death or CP, whereas with risks for CLD exceeding 65%, it reduced this chance. Conclusions. The effect of postnatal corticosteroids on the combined outcome of death or CP varies with the level of risk for CLD.

High-Flow Nasal Cannulae in Very Preterm Infants after Extubation

BACKGROUND The use of high-flow nasal cannulae is an increasingly popular alternative to nasal continuous positive airway pressure (CPAP) for noninvasive respiratory support of very preterm infants (gestational age, <32 weeks) after extubation. However, data on the efficacy or safety of such cannulae in this population are lacking. METHODS In this multicenter, randomized, noninferiority trial, we assigned 303 very preterm infants to receive treatment with either high-flow nasal cannulae (5 to 6 liters per minute) or nasal CPAP (7 cm of water) after extubation. The primary outcome was treatment failure within 7 days. Noninferiority was determined by calculating the absolute difference in the risk of the primary outcome; the margin of noninferiority was 20 percentage points. Infants in whom treatment with high-flow nasal cannulae failed could be treated with nasal CPAP; infants in whom nasal CPAP failed were reintubated. RESULTS The use of high-flow nasal cannulae was noninferior to the use of nasal CPAP, with treatment failure occurring in 52 of 152 infants (34.2%) in the nasal-cannulae group and in 39 of 151 infants (25.8%) in the CPAP group (risk difference, 8.4 percentage points; 95% confidence interval, -1.9 to 18.7). Almost half the infants in whom treatment with high-flow nasal cannulae failed were successfully treated with CPAP without reintubation. The incidence of nasal trauma was significantly lower in the nasal-cannulae group than in the CPAP group (P=0.01), but there were no significant differences in rates of serious adverse events or other complications. CONCLUSIONS Although the result for the primary outcome was close to the margin of noninferiority, the efficacy of high-flow nasal cannulae was similar to that of CPAP as respiratory support for very preterm infants after extubation. (Funded by the National Health and Medical Research Council; Australian New Zealand Clinical Trials Network number, ACTRN12610000166077.).

Effect of Sustained Inflation Length on Establishing Functional Residual Capacity at Birth in Ventilated Premature Rabbits

The effect of inflation length on lung aeration pattern, tidal volumes, and functional residual capacity (FRC) immediately after birth was investigated. Preterm rabbits (28 d), randomized into four groups, received a 1-, 5-, 10-, or 20-s inflation (SI) followed by ventilation with 5 cm H2O end-expiratory pressure. Gas volumes were measured by plethysmography and uniformity of lung aeration by phase contrast x-ray imaging for 7 min. The first inspiratory volume significantly (p < 0.001) increased with inflation duration from a median (IQR) of 0.2 (0.1–3.1) mL/kg for 1-s inflation to 23.4 (19.3–30.4) mL/kg for 20-s SI. The lung was uniformly aerated, and the FRC and tidal volume fully recruited after 20-s SI. A 10-s SI caused a higher FRC (p < 0.05) at 7 min, and a 20-s SI caused a higher FRC (p < 0.05) at 20 s and 7 min than a 1- or 5-s SI. The mean (SD) time for 90% of the lung to aerate was 14.0 (4.1) s using 35 cm H2O peak inflation pressure. In these rabbits, 10- and 20-s SI increased the inspiratory volume and produced a greater FRC, and a 20-s SI uniformly aerated the lung before ventilation started.

From liquid to air: breathing after birth.

The first breaths after birth are characterized by a rapid transition from liquid- to air-filled lungs. Air is drawn into the lung during inspiration, and some remains at end expiration to establish an end-expiratory gas volume or functional residual capacity (FRC). This is usually marked by a cry, often misinterpreted as a protest from the baby. Some infants, especially those born preterm, require respiratory support during this transitional phase. To do this effectively, we need to understand the normal physiological processes occurring at this time. Sometimes it can be difficult to aerate the lungs of preterm infants with intermittent positive pressure ventilation with pressures recommended in international guidelines, particularly when the infant does not breathe and aeration is completely dependent on the inflation pressures. Studies have shown that intermittent positive pressure ventilation should be performed without high tidal volumes to avoid damaging the lung while establishing the FRC. 1,2 However, since the use of antenatal steroids, more very preterm infants breathe spontaneously at birth, only requiring support from nasal continuous positive airway pressure. Understanding the normal spontaneous breathing pattern after birth is essential for developing safe, efficient ventilatory strategies when breathing is inadequate. Numerous physiological studies immediately after birth of spontaneously breathing infants were published between 1960 and 1986. 3-10 However, little new data are currently available on this topic, reflecting the difficulties of performing these studies. This review will discuss what happens during the first breaths of air with the emphasis on where the liquid goes and the current knowledge about the spontaneous breathing pattern adopted by infants immediately after birth.

Oxygen saturation and heart rate during delivery room resuscitation of infants <30 weeks gestation with air or 100% oxygen.

Background: Because of concerns about harmful effects of 100% oxygen on newborn infants, air has started to be used for resuscitation in the delivery room. Objective: To describe changes in preductal oxygen saturation (Spo2) and heart rate (HR) in the first 10 min after birth in very preterm infants initially resuscitated with 100% oxygen (OX100) or air (OX21). Patients and methods: In July 2006, policy changed from using 100% oxygen to air. Observations of Spo2 and HR before and after the change were recorded whenever a member of the research team was available to attend the birth. Results: There were 20 infants in the OX100 group and 106 in the OX21 group. In the OX100 group, Spo2 had risen to a median of 84% after 2 min and 94% by 5 min. In the OX21 group, median Spo2 was 31% at 2 min and 54% at 5 min. In the OX21 group, 92% received supplemental oxygen at a median of 5 min; the Spo2 rose to a median of 81% by 6 min. In the first 10 min after birth, 80% and 55% of infants in the OX100 and OX21 groups, respectively, had an Spo2 ⩾95%. Increases in HR over the first 10 min were very similar in the two groups. Conclusions: Most very preterm infants received supplemental oxygen if air was used for the initial resuscitation. In these infants, the use of backup 100% oxygen and titration against Spo2 resulted in a similar course to “normal” term and preterm infants. Of the infants resuscitated with 100% oxygen, 80% had Spo2 ⩾95% during the first 10 min. The HR changes in the two groups were very similar.