Vishal S. Kapadia

Part 13: Neonatal Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

The following guidelines are a summary of the evidence presented in the 2015 International Consensus on Cardiopulmo nary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations (CoSTR).1,2 Throughout the online version of this publication, live links are provided so the reader can connect directly to systematic reviews on the International Liaison Committee on Resuscitation (ILCOR) Scientific Evidence Evaluation and Review System (SEERS) website. These links are indicated by a combination of letters and numbers (eg, NRP 787). We encourage readers to use the links and review the evidence and appendices. These guidelines apply primarily to newly born infants transitioning from intrauterine to extrauterine life. The recommendations are also applicable to neonates who have completed newborn transition and require resuscitation during the first weeks after birth.3 Practitioners who resuscitate infants at birth or at any time during the initial hospitalization should consider following these guidelines. For purposes of these guidelines, the terms newborn and neonate apply to any infant during the initial hospitalization. The term newly born applies specifically to an infant at the time of birth.3 Immediately after birth, infants who are breathing and crying may undergo delayed cord clamping (see Umbilical Cord Management section). However, until more evidence is available, infants who are not breathing or crying should have the cord clamped (unless part of a delayed cord clamping research protocol), so that resuscitation measures can commence promptly. Approximately 10% of newborns require some assistance to begin breathing at birth. Less than 1% require extensive resuscitation measures,4 such as cardiac compressions and medications. Although most newly born infants successfully transition from intrauterine to extrauterine life without special help, because of the large total number of births, a significant number will require some degree of resuscitation.3 Newly born infants who do not …

Resuscitation of Preterm Neonates With Limited Versus High Oxygen Strategy

OBJECTIVE: To determine whether a limited oxygen strategy (LOX) versus a high oxygen strategy (HOX) during delivery room resuscitation decreases oxidative stress in preterm neonates. METHODS: A randomized trial of neonates of 24 to 34 weeks’ gestational age (GA) who received resuscitation was performed. LOX neonates received room air as the initial resuscitation gas, and fraction of inspired oxygen (Fio2) was adjusted by 10% every 30 seconds to achieve target preductal oxygen saturations (Spo2) as described by the 2010 Neonatal Resuscitation Program guidelines. HOX neonates received 100% O2 as initial resuscitation gas, and Fio2 was adjusted by 10% to keep preductal Spo2 at 85% to 94%. Total hydroperoxide (TH), biological antioxidant potential (BAP), and the oxidative balance ratio (BAP/TH) were analyzed in cord blood and the first hour of life. Secondary outcomes included delivery room interventions, respiratory support on NICU admission, and short-term morbidities. RESULTS: Forty-four LOX (GA: 30 ± 3 weeks; birth weight: 1678 ± 634 g) and 44 HOX (GA: 30 ± 3 weeks; birth weight: 1463 ± 606 g) neonates were included. LOX decreased integrated excess oxygen (∑Fio2 × time [min]) in the delivery room compared with HOX (401 ± 151 vs 662 ± 249; P < .01). At 1 hour of life, BAP/TH was 60% higher for LOX versus HOX neonates (13 [9–16] vs 8 [6–9]) µM/U.CARR, P < .01). LOX decreased ventilator days (3 [0–64] vs 8 [0–96]; P < .05) and reduced the incidence of bronchopulmonary dysplasia (7% vs 25%; P < .05). CONCLUSIONS: LOX is feasible and results in less oxygen exposure, lower oxidative stress, and decreased respiratory morbidities and thus is a reasonable alternative for resuscitation of preterm neonates in the delivery room.

The NLRP3 inflammasome is critically involved in the development of bronchopulmonary dysplasia

The pathogenesis of bronchopulmonary dysplasia (BPD), a devastating lung disease in preterm infants, includes inflammation, the mechanisms of which are not fully characterized. Here we report that the activation of the NLRP3 inflammasome is associated with the development of BPD. Hyperoxia-exposed neonatal mice have increased caspase-1 activation, IL1β and inflammation, and decreased alveolarization. Nlrp3(-/-) mice have no caspase-1 activity, no IL1β, no inflammatory response and undergo normal alveolarization. Treatment of hyperoxia-exposed mice with either IL1 receptor antagonist to block IL1β or glyburide to block the Nlrp3 inflammasome results in decreased inflammation and increased alveolarization. Ventilated preterm baboons show activation of the NLRP3 inflammasome with increased IL1β:IL1ra ratio. The IL1β:IL1ra ratio in tracheal aspirates from preterm infants with respiratory failure is predictive of the development of BPD. We conclude that early activation of the NLRP3 inflammasome is a key mechanism in the development of BPD, and represents a novel therapeutic target for BPD.

Perinatal Asphyxia with Hyperoxemia within the First Hour of Life Is Associated with Moderate to Severe Hypoxic-Ischemic Encephalopathy

OBJECTIVE To determine whether early hyperoxemia in neonates with severe perinatal acidemia is associated with the development of hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN We identified 120 infants at ≥ 36 weeks gestational age with perinatal acidosis born at Parkland Hospital who qualified for a screening neurologic exam for cooling therapy. Based on a PaO2 measurement during the first hour of life, the cohort was divided into infants with hyperoxemia (PaO2 >100 mmHg) and those without hyperoxemia (PaO2 ≤ 100 mmHg). The rate of moderate-severe encephalopathy was compared between the groups using χ(2) analysis, as well as multiple logistic regression, taking into account baseline characteristics and confounding variables. RESULTS Thirty-six infants (30%) had an initial PaO2 >100 mmHg. Infants with and without hyperoxemia had similar baseline maternal and infant characteristics. Infants with hyperoxemia had a higher incidence of HIE than those without hyperoxemia (58% vs 27%; P = .003). Admission hyperoxemia was associated with a higher risk of HIE (OR, 4; 95% CI, 1.4-10.5; adjusted P = .01). Among the neonates with moderate-severe HIE during the first 6 hours of life, those with hyperoxemia had a higher incidence of abnormal brain magnetic resonance imaging results, consistent with hypoxic ischemic injury, compared with those without hyperoxemia (79% vs 33%; P = .015). CONCLUSION In neonates with perinatal acidemia, admission hyperoxemia is associated with a higher incidence of HIE. Among neonates with HIE, admission hyperoxemia is associated with abnormal brain magnetic resonance imaging findings. The judicious use of oxygen during and after resuscitation is warranted.

Part 13: Neonatal resuscitation 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care (Reprint)

Reprint: The American Heart Association requests that this document be cited as follows: Wyckoff MH, Aziz K, Escobedo MB, Kapadia VS, Kattwinkel J, Perlman JM, Simon WM, Weiner GM, Zaichkin, JG. Part 13: neonatal resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015;132(suppl 2):S543–S560. Reprinted with permission of the American Heart Association, Inc. This article has been co-published in Circulation . The following guidelines are a summary of the evidence presented in the 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations (CoSTR).1,2 Throughout the online version of this publication, live links are provided so the reader can connect directly to systematic reviews on the International Liaison Committee on Resuscitation (ILCOR) Scientific Evidence Evaluation and Review System (SEERS) website. These links are indicated by a combination of letters and numbers (eg, NRP 787). We encourage readers to use the links and review the evidence and appendices. These guidelines apply primarily to newly born infants transitioning from intrauterine to extrauterine life. The recommendations are also applicable to neonates who have completed newborn transition and require resuscitation during the first weeks after birth.3 Practitioners who resuscitate infants at birth or at any time during the initial hospitalization should consider following these guidelines. For purposes of these guidelines, the terms newborn and neonate apply to any infant during the initial hospitalization. The term newly born applies specifically to an infant at the time of birth.3 Immediately after birth, infants who are breathing and crying may undergo delayed cord clamping (see Umbilical Cord Management section). However, until more evidence is available, infants who are not breathing or crying should have the cord clamped (unless part of a delayed cord clamping research protocol), so that resuscitation measures can …

Chest Compressions for Bradycardia or Asystole in Neonates

When effective ventilation fails to establish a heart rate of greater than 60 bpm, cardiac compressions should be initiated to improve perfusion. The 2-thumb method is the most effective and least fatiguing technique. A ratio of 3 compressions to 1 breath is recommended to provide adequate ventilation, the most common cause of newborn cardiovascular collapse. Interruptions in compressions should be limited to not diminishing the perfusion generated. Oxygen (100%) is recommended during compressions and can be reduced once adequate heart rate and oxygen saturation are achieved. Limited clinical data are available to form newborn cardiac compression recommendations.

Higher or lower oxygen for delivery room resuscitation of preterm infants below 28 completed weeks gestation: a meta-analysis

Objective To systematically review outcomes of infants ≤28+6 weeks gestation randomised to resuscitation with low (≤0.3) vs high (≥0.6) fraction of inspired oxygen (FiO2) at delivery. Design Systematic review of randomised controlled trials of low (≤0.3) vs high (≥0.6) FiO2 resuscitation. Information was obtained from databases (Medline/Pub Med, EMBASE, ClinicalTrials.gov, Cochrane) and meeting abstracts between 1990 to 2015. Search index terms: preterm/ resuscitation/oxygen. Data for infants ≤28+6 weeks gestation were independently extracted and pooled using a random effects model. Analyses were performed with Revman V.5. Main outcome measures Death in hospital, bronchopulmonary dysplasia (BPD), retinopathy of prematurity >grade 2 (ROP), intraventricular haemorrhage >grade 2 (IVH), patent ductus arteriosus (PDA) and necrotising enterocolitis (NEC). Results A total of 251 and 253 infants were enrolled in 8 studies (6 masked, 2 unmasked) in the lower and higher oxygen groups, respectively, (mean gestation 26 weeks) between 2005 and 2014. There were no differences in BPD (relative risk, 95% CIs 0.88 (0.68 to 1.14)), IVH (0.81 (0.52 to 1.27)), ROP (0.82 (0.46 to 1.46)), PDA (0.95 (0.80 to 1.14)) and NEC (1.61 (0.67 to 3.36)) and overall mortality (0.99 (0.52 to 1.91)). Mortality was lower in low oxygen arms of masked studies (0.46 (0.23 to 0.92), p=0.03) and higher in low oxygen arms of unmasked studies (1.94 (1.02 to 3.68), p=0.04). Conclusions There is no difference in the overall risk of death or other common preterm morbidities after resuscitation is initiated at delivery with lower (≤0.30) or higher (≥0.6) FiO2 in infants ≤28+6 weeks gestation. The opposing results for masked and unmasked trials may represent a Type I error, emphasising the need for larger, well designed studies.

Prenatal closure of the ductus arteriosus and maternal ingestion of anthocyanins

Prenatal closure of the ductus arteriosus (DA) is associated with maternal ingestion of cyclooxygenase inhibitors during pregnancy. We report a case of prenatal DA closure after maternal ingestion of MonaVie, a juice blend containing the cyclooxygenase and nitric oxide synthase inhibitors anthocyanins and proanthocyanidins. A G2P0Ab1 woman had an uncomplicated first and second trimester and normal 20-week fetal ultrasound. At 37 weeks, she developed polyhydramnios; a fetal echocardiogram showed right atrial and ventricular (RV) enlargement with RV dysfunction. Immediately after birth, there was pulmonary hypertension by echocardiogram with DA closure, severe RV hypertrophy and dysfunction, and marked right-to-left atrial shunting. Improvement occurred over 3 weeks with the neonate tolerating room air and a follow-up echocardiogram showing minimal atrial shunting and improved RV function. This report shows an association between MonaVie ingestion throughout pregnancy and prenatal DA closure resulting in cardiac dysfunction and pulmonary hypertension at birth.

Drugs during delivery room resuscitation – What, when and why?

Although seldom needed, the short list of medications used for delivery room resuscitation of the newborn includes epinephrine and volume expanders. Naloxone, sodium bicarbonate and the use of other vasopressors are no longer considered helpful during acute resuscitation and are more often administered in the post-resuscitative period under special circumstances. This review examines the existing literature for the two commonly used medications in neonatal resuscitation and identifies the many knowledge gaps requiring further research.

Outcomes of oxygen saturation targeting during delivery room stabilisation of preterm infants

Objective To determine the association between SpO2 at 5 min and preterm infant outcomes. Design Data from 768 infants <32 weeks gestation from 8 randomised controlled trials (RCTs) of lower (≤0.3) versus higher (≥0.6) initial inspiratory fractions of oxygen (FiO2) for resuscitation, were examined. Setting Individual patient analysis of 8 RCTs Interventions Lower (≤0.3) versus higher (≥0.6) oxygen resuscitation strategies targeted to specific predefined SpO2 before 10 min of age. Patients Infants <32 weeks gestation. Main outcome measures Relationship between SpO2 at 5 min, death and intraventricular haemorrhage (IVH) >grade 3. Results 5 min SpO2 data were obtained from 706 (92%) infants. Only 159 (23%) infants met SpO2 study targets and 323 (46%) did not reach SpO280%. Pooled data showed decreased likelihood of reaching SpO280% if resuscitation was initiated with FiO2 <0.3 (OR 2.63, 95% CI 1.21 to 5.74, p<0.05). SpO2 <80% was associated with lower heart rates (mean difference −8.37, 95% CI −15.73 to –1.01, *p<0.05) and after accounting for confounders, with IVH (OR 2.04, 95% CI 1.01 to 4.11, p<0.05). Bradycardia (heart rate <100 bpm) at 5 min increased risk of death (OR 4.57, 95% CI 1.62 to 13.98, p<0.05). Taking into account confounders including gestation, birth weight and 5 min bradycardia, risk of death was significantly increased with time taken to reach SpO280%. Conclusion Not reaching SpO280% at 5 min is associated with adverse outcomes, including IVH. Whether this is because of infant illness or the amount of oxygen that is administered during stabilisation is uncertain and needs to be examined in randomised trials